Curriculum Vitae

Prof. Dr. Karl Helmut Grubmuller¨ Office: Max-Planck-Institute for Biophysical Chemistry Theoretical Molecular Biophysics Group Am Faßberg 11, 37077 Göttingen, Germany +49(0)551-201-2301/-2300, [email protected] Home: Minkowskiweg 10 37077 Göttingen, +49-551-531 78 68

Born July 31, 1965, Munich, Germany

Education: 2002 Habilitation, venia legendi for Physics, University of G¨ottingen, 1994 Doctorate, summa cum laude, Technical University of Munich 1991–1993 Physics Department, Munich; since 1993 Theoretical Biophysics Group, Ludwig-Maximilians-University, Munich (supervisor: Prof. Paul Tavan), PhD Thesis “Molecular Dynamics of Proteins at Long Time Scales” 1990 Diploma (ﬁnal examination) 1989–1990 Physics Department, Munich (supervisor: Prof. Klaus Schulten), diploma thesis “Dynamics Simulation of Very Large Macromolecules with a Parallel Computer” 1985–1990 Technical University of Munich, study of physics

Professional Record: 2005– Honorary Professor for Physics, University of Göttingen 2003– Director, Max-Planck-Institute for Biophysical Chemistry, Göttingen Head of the Theoretical and Computational Biophysics Department 2003 Associate Professor for Biomolecular Sciences at the Ecole´ Polytechnique Fédérale de Lausanne (EPFL) 1998–2003 Head of the Theoretical Molecular Biophysics Group at the Max Planck Institute for Biophysical Chemistry, Göttingen 1997 EMBO fellow at the Institute for Molecular Biology and Biophysics, Federal Institute of Technology (ETH) Zurich, Switzerland 1994–1996 Research visits at the Laboratoire de Biophysique Moleculaire et Cellulaire, CENG, Grenoble, France 1994–1998 Postdoctoral assistant at the Theoretical Biophysics Group, University of Munich 1990/1991 Research visits at the Theoretical Biophysics Group, Beckman Institute, University of Illinois at Urbana/Champaign, U.S.A.

1 Summary

Research Interests: Theory and simulation of biomolecular structure, dynamics, and function

72 publications, 34 publications in Refereed International Journals 155 talks given, 65 invited talks at Conferences and Workshops Max Planck Society, Scientiﬁc Member German Science Foundation (DFG), Member of the Reviewing Panel European Biophysical Socienties’ Association (EBSA), Executive Committee Member Biophysical Journal, Editorial Board Member Current Nanoscience, Editorial Board Member Biointerphases, Editorial Board Member Current Chemical Biology, Editorial Board Member Referee assistance for 40+ Journals and 11 funding agencies, ca. 50 reports per year Member of 4 appointment committees Organized 12 conferences and workshops Grants approved: ca. 5.5 Mio 11 years’ teaching experience 24 supervised Theses

2 Research Accomplishments of H.G. and Co-workers

First molecular dynamics simulation of water permeation through aquaglyceroporins · Reﬁned aquaporin structure from cryo electron microscopy · Explained aquaporin proton ﬁlter mechanism · Accurate computation of water permeation rates

First force probe MD simulation of mechanical energy transfer in F1 ATPase

First molecular dynamics simulation of single molecule force probe experiments · First calculation of unbinding forces · Atomic model for streptavidin/biotin unbinding mechanism · Atomic model for antibody/antigen (AN02/hapten) unbinding mechanism · Microscopic explanation of elastic properties of polysaccharides

Statistical mechanics of single molecule experiments · Developed method to reconstruct energy landscapes from dynamic force spectroscopy · Developed method to extract conformational motions from single molecule FRET

Contributions to the statistical mechanics of conformational substates and the structural dynamics of proteins · First method to predict slow (µs) conformational transitions · Developed method to predict chemical reaction pathways · Developed deﬁnition of conformational substates as free energy minima · Deﬁned relevant conformational degrees of freedom · Structural interpretation of taxonomic myoglobin substates at the atomic level · Systematic characterization of reversible peptide folding dynamics

Conformational plasticity of membrane fusion proteins · Calculated thermodynamic stability of SNARE protein mutants

· Calculated structure and mechanical properties of SNARE linker region

Co-author of EGO, a very eﬃcient molecular dynamics code · Developed eﬃcient molecular dynamics methods · Problem-oriented evaluations of molecular dynamics methods

Author of SOLVATE, a program to generate physiological explicit solvent models Author of FretTrace, a program for maximum likelihood interprestation of FRET data

Contributions to parallel computing · Built ﬁrst parallel computer used for molecular dynamics simulations · First eﬃcient parallel molecular dynamics program

3 Current Position Director at the Max-Planck-Institute for Biophysical Chemistry, G¨ottingen, Germany Head of the Theoretical and Computational Biophysics Department

Positions Oﬀered but not accepted 2002: Professor (C4) in Theoretical Biophysics, Dusseldorf¨ University 2001: Head of Theoretical Biophysics Research Group, Julic¨ h Research Center

Professional Memberships Max Planck Society German Science Foundation (DFG, elected member of the review board 2003–) Fritz Haber Minerva Research Center for Molecular Dynamics (member of the advisory board 2005–) European Biophysical Socienties’ Association (EBSA, Executive Committee Member 2005–) German Biophysical Society, DGfB (Panel Member 1997–2000) German Physical Society, DPG Biophysical Society (U.S.A.) American Association for the Advancement of Science (AAAS) G¨ottingen Computer Center (GWDG) Scientiﬁc Advisory Board

Editorial Board Member Biophysical Journal (2002–) Current Nanoscience (2004–)

Biointerphases (2006–)

Current Chemical Biology (2006–)

Referee assistance for Journals (Currently ca. 50 reports per year) Nature Science Nature Struct. Biol. Nature Materials Nature Biotechnology Proc. Natl. Acad. Sci., U.S.A. Physical Review Letters Biophysical Journal Angewandte Chemie, Intl. Ed. Journal of the American Chemical Society (JACS) Biochemistry

4 Journal of Molecular Biology Biopolymers EMBO reports Journal of Chemical Physics Journal of Physical Chemistry Chem. Phys. Chem. Chem. Bio. Chem. Chemistry – A Europ. J. Biophysical Chemistry Journal of Medicinal Chemistry Biochimica Biophysica Acta (BBA) Proteins Structure, Function and Genetics European Biophysical Journal FEBS Letters Structure The European Physical Journal Europhysics Letters Journal of Biological Inorganic Chemistry Journal of Chemical Physics and Physical Chemistry Journal of Computational Physics Journal of Computational Chemistry Journal of Structural Biology Journal of Molecular Modeling Biological Chemistry Computer Physics Communications SIAM Journal on Scientiﬁc Computing Journal of Biomolecular Structure and Dynamics Supramolecular Science Zeitschrift fur¨ Physikalische Chemie (Intl. Ed.) Journal of Theoretical Biology Polymer and Cell Dynamics: Multicsale Modeling and Numerical Simulations Lecture Notes in Computational Science and Engineering

Referee assistance for Funding Agencies Deutsche Forschungsgemeinschaft (DFG; member of the review board), Germany Depertment of Energy (DOE), U.S.A. Schweizerischer Nationalfonds, Switzerland European Science Foundation (ESF) Engineering and Physical Sciences Research Council, UK Biotechnology and Biological Sciences Research Council, UK Dutch National Science Foundation (NWO), NL Fonds voor Wetenschappelijk Onderzoek – Vlaanderen (FWO), NL The Israel Science Foundation Minerva-Weizmann Foundation

5 Boehringer Ingelheim Fonds

Member of Appointment Committees Max-Planck-Institute for Molecular Physiology, Dortmund Max-Planck-Institute for the Dynamics of Complex Systems, Magdeburg Saarland University, Theoretical Physics Max-Planck-Society, Grundungsk¨ ommission Centre for Free Electron Laser Studies (CFEL)

Organized Conferences, Meetings, and Seminars Summer School ’Nanostudienwoche’, Swiss Study Foundation, Engelberg, Switzerland, Aug. 2005, 14 participants

5. Workshop Computer Simulation and Theory of Biomolecules, Kloster Hunfeld,¨ Ger- many, May 2005 4. Workshop Computer Simulation and Theory of Biomolecules, Kloster Hunfeld,¨ Ger- many, May 2004 John von Neumann Winter School Computational Soft Matter: From Synthetic Polymers to Proteins, Gustav-Stresemann-Institute, Bonn, Germany, March 2004 3. Workshop Computer Simulation and Theory of Biomolecules, Kloster Hunfeld,¨ Ger- many, May 2003 1. Workshop Methods in Biomolecular Simulation, Schloss Ringberg, Germany, April 2003 2. Workshop Computer Simulation and Theory of Biomolecules, Kloster Hunfeld,¨ Ger- many, April 2002, ca. 90 participants Aquaplugs EU meeting, Göttingen, Oct. 19–20 (2001) 1. Workshop Computer Simulation and Theory of Biomolecules, Kloster Hunfeld,¨ Ger- many, May 2001, ca. 40 participants Meeting of the VW-Foundation, Conformational Control of Biomolecular Functions, Kloster Banz, Staffelstein, Germany, June 2000, ca. 90 participants Summer School ’Bioinformatics’, Swiss Study Foundation, Montezillon, Neuchâtel, Switzerland, Aug. 1999, 12 participants, co-organized with Andreas Engel (Univ. Basel) Joint Meeting of the Dutch and German Biophysical Societies and the Biochemistry and Molecular Biology Society, Structural Heterogeneity and Dynamics of Biological Macro- molecules, Hunfeld,¨ May 1999, 98 participants Bi-weekly Seminar for PhD Students and Postdocs at the Max-Planck Institute for Bio- physical Chemistry, Göttingen, since 2000, ca. 50 participants

6 Program Committee Member

Jahrestagung der Deutschen Biophysikalischen Gesellschaft, Munster,¨ Oct. 2001 Workshop “Computersimulation von Biomolekulen”,¨ Hunfeld,¨ May 2001 Conformational Control of Biomolecular Functions, Staﬀelstein, June 2000 Jahrestagung der Deutschen Biophysikalischen Gesellschaft, Ulm, Oct. 1999 Structural Heterogeneity and Dynamics of Biological Macromolecules, Hunfeld,¨ May 1999

Grants EU (Pathﬁnder STREP project), 2005 NANOMOT: Synthetic Biomimetic Nanoengines: ... 2 250 000 Volkswagenstiftung, priority area, 2005 Generalized dynamics beyond molecular dynamics ... 189 000 IT-Programme of the Max Planck Society, 2004 310 000 EU (STREP-project) , 2004 Validation of the Plasmodium aquaglyceroporin as a drug target 160 000 Human Frontier Science Program, 2004 Exploring Structural Changes and Energy Landscapes of Nuclear Pores and Complexes during Function 300 000 Volkswagenstiftung, priority area, 2003 Investigating komplex folding and misfolding mechanisms ... 114 900 Volkswagenstiftung, priority area, 2002 Nanomechanics and dynamics of initial steps in membrane fusion (cont.) 58 000 DFG (Sonderforschungsbereich 357), 2001 Kinetik und Verzweigungsverh¨altnisse unimolarer Reaktionen 74 000 EU (Quality of Life Programme), 2000 Antidiuretics using Vasopressin-V2-Receptor Agonists 254 000 EU (Biotech RDT action), 2000 AQUAPLUGS: Structure and function of aquaporins; inhibitor design 251 000 MPG, BAR1, 2000 (with T. Jovin) Setup of an interactive molecular virtual reality environment 106 000 DFG, Normalverfahren (cont. proposal), 1999 Simulation and interpretation of AFM antigen-binding experiments 92 000 Volkswagenstiftung, priority area, 1999 Nanomechanics and dynamics of initial steps in membrane fusion 89 000 EU (Biotech RDT action), 1998 MIP-Family: Structure and function of aquaporin 1 176 000

1Beratender Ausschuß fur¨ Rechenanlagen der Max-Planck-Gesellschaft / Advisory Board for computer equipment

7 Volkswagenstiftung, Junior Group Application, 1997 Conformational heterogeneity and dynamics of proteins 716 000 EMBO-Fellowship, 1997 Prediction of pathologic conformational motions in prions 8 000 DFG (Sonderforschungsbereich 533, with P. Tavan), 1996 Theory and computer simulation of protein conformational dynamics 327 000 DFG, priority area,1996 Simulation and interpretation of AFM antigen-binding experiments 88 000 PROCOPE/DAAD, 1993 & 1995 Studies of ion transport through gramicidin channels (three research visits granted) Several proposals for computer time (MPI Martinsried, MPI Garching, KFA Julic¨ h, Univ. Stuttgart)

8 Collaborations

Simulation and interpretation of single molecule force probe experiments Hermann Gaub, Matthias Rief (Univ. Munich, Germany) Vincent Moy (Univ. Miami, USA) Peter Hinterdorfer (Univ. Linz, Austria) Hongbin Li (Mayo Clinics, Rochester, USA) Suzanne Jarvis (Nanotechnol Research Institute, Tsukuba, Japan) Dieter Oesterhelt (MPI for biochemistry, Martinsried, Germany) Hualiang Jiang (Drug Discovery Cent., Chinese Acad. of Sciences, Shanghai, China) Mathias Gautel (King’s College, London, United Kingdom) Ziv Reich (Weizmann Institute, Rehovot, Israel) Roland Netz (Univ. Munich, Germany)

Conformational plasticity and mechanical properties of SNARE proteins Reinhard Jahn, Dirk Fasshauer (MPI for biophysical chemistry, G¨ottingen, Germany) Martin Margittai (University of Southern California, USA) Ernst-Ludwig Florin (Univ. Austin, Texas, USA) Erwin Neher (MPI for biophysical chemistry, G¨ottingen, Germany)

Hybrid MD/QM simulations of monomolecular dissociation reactions Michele Parrinello (ETH Zurich and CSCS, Manno) Dominik Marx (Ruhr-Univ. Bochum, Germany) Armin de Meijere, oligospirocyclopropane-systems (Univ. G¨ottingen, Germany) Roger Rousseau (Condensed Matter Group, SISSA, Trieste, Italy) Carme Rovira (Univ. de Barcelona, Spain)

Conformational ﬂexibility of Myoglobin Jeﬀrey Evanseck (Duquesne University, USA) Brita Schulze (MBT Munich Biotechnology GmbH, Germany)

Mechanical energy transfer in F1-ATPase Wolfgang Junge (Univ. Osnabruc¨ k, Germany)

Dielectric properties of aqueous solutions Udo Kaatze (Univ. G¨ottingen, Germany)

Reversible peptide folding dynamics

9 Xavier Daura (ETH Zurich, Switzerland) Wilfred van Gunsteren (ETH Zurich, Switzerland) Alan E. Mark (Univ. Groningen, The Netherlands)

Protein folding simulations Vijay S. Pande (Stanford Univ., USA)

Processive enzymatic mechanism of hyaluronate lyase Luciane Vieira de Mello, (Cenargen/Embrapa, Brasilia, Brazil) Mark Jedrzejas (Children’s Hospital Oakland Research Institute, Oakland, USA)

Reﬁnement, function, and regulation of aquaporins Andreas Engel (Biocenter, Univ. Basel, Switzerland) Henning Stahlberg (Univ. California, Davis, USA) Peter Deen (Nijmegen Univ., The Netherlands) J. Bernard Heymann (Caltech, Pasadena, USA) Sabine Flitsch (Edinburgh Univ., United Kingdom) Soren Nielsen (Aarhus Univ., Denmark) Stefan Hohmann (Goteborg Univ., Sweden) Kaoru Mitsuoka (Kyoto University, Japan) Yoshinori Fujiyoshi (Kyoto Univ., Japan) Volkhard Helms (Univ. Saarbruc¨ ken)

Voltage clamp permeation assays and Simulation of Gramicidin Peter Pohl (Forschungsinstitut fur¨ Molekulare Pharmakologie, Berlin) Peter Tieleman (Calgary Univ., Canada) Serge Crouzy, Yves Chapron (Molecular Biophysics, CEA Grenoble, France)

NMR structure reﬁnement and structure prediction with CONCOORD Gerrit Vriend, Chris Spronk (CMBI, Nijmegen Univ., The Netherlands)

Conformational heterogeneity of neurotensin compared to solid state NMR Marc Baldus (MPI for Biophysical Chemistry, G¨ottingen)

Simulation of Lipid Membranes and Vesicle Dynamics Alan Mark, Siewert-Jan Marrink, Volker Knecht (Groningen Univ., The Netherlands) Tim Salditt (Univ. G¨ottingen, Germany) Georg Pabst (Austrian Academy of Sciences, Graz, Austria) Eberhard Neumann (Bielefeld Univ., Germany)

10 Thomas Heimburg (Niels Bohr Instutute, Copenhagen, Denmark)

Dynamics of peptides bound to the major human histocompatibility complex (MHC I) Ulrike Alexiev (Freie Universit¨at Berlin, Germany) Andreas Ziegler, Barbara Uchanska-Ziegler (Charitee, Humboldt Univ. Berlin)

Simulation of Single Molecule Spectroscopy Claus Seidel (Univ. Dusseldorf,¨ Germany) Filipp Oesterhelt (Univ. Dusseldorf,¨ Germany) Reinhard Luhrmann¨ (MPI for biophysical chemistry, Göttingen, Germany) Jurgen¨ Troe (MPI for biophysical chemistry, Göttingen, Germany) Ulrike Alexiev (Freie Universität Berlin, Germany) Ben Schuler (Univ. Zuric¨ h, Switzerland)

Interactive virtual force probe molecular dynamics Tom Jovin, Reinhard Klement (MPI for biophysical chemistry, G¨ottingen, Germany)

Dynamics of small DNA-strands Christian Griesinger (MPI for biophysical chemistry, G¨ottingen, Germany)

Parallel Molecular Dynamics Algorithms Helmut Heller (Leibniz Comnputer Center, Munich, Germany)

Teaching Experience

Biophysics I (2004/2005) Computational Biomolecular Dynamics (2004/2005) Theoretical Molecular Biophysics II (2004) Theoretical Molecular Biophysics I (2003/2004) Theoretical Molecular Biophysics II (2003) Theoretical Molecular Biophysics I (2002/2003) Contribution to Hands-on practical ’Biophysics’ for students (2001,2002) Seminar for PhD Students and Postdocs (2000–) Summer School ’Bioinformatics’, Neuchˆatel, Switzerland (1999) Hands-on physics exercises for advanced students, (1997/98) Theoretical Physics I: Mechanics, Tutorials (1996/97) Self-organizing Neural Networks, Seminar (1996) Theoretical Molecular Physics, Tutorials (1995/96) Computational Physics, Tutorials (1995/96)

11 Theoretical Biophysics: Stochastic Processes II, Tutorials (1995) Theoretical Biophysics: Stochastic Processes I, Tutorials (1994/95) Self-organizing Neural Networks, Seminar (1994) Theoretical Molecular Physics, Tutorials (1993/94)

Supervised Theses Martin Meling (Dipl., 2005–): Mechanical properties of spider silk polyamides Christian Kappel (Dipl., 2005–): Mechanical unfolding of membrane proteins Ulf Hensen (PhD, 2004–): Conformational motions of pyrovate kinase Maik Götte (PhD, 2004–): Kinase inhibitor design Martin Stumpe (PhD, 2003–): Urea-induced unfolding of proteins Lars Schäfer (PhD, 2003–): Monomolecular dissociation reactions in condensed phase Friedemann Reinhard (Dipl., 2003–2004): Entropy of solvation shells Frauke Gräter (PhD, 2002–2005): Mechanically induced titin kinase activation Oliver Lange (PhD, 2002–2005): Generalized Langevin Models of Protein Dynamics Oliver Slawik (PhD, 2001–): Virtual Reality in Molecular Dynamics Simulations Gunnar Schröder (PhD, 2000–2004): Simulation of protein FRET spectra Jr-Hung Lin (Dipl., 2000–2001): Dielectric Properties of Aqueous Solutions Volker Knecht (PhD, 1999–2003): Conformational Flexibility of the SNARE Complex Rainer Böckmann (PhD, 1998–2002): From α helices to the ATP Synthase Matthias Muller¨ (PhD, 1998–2001): Catalytic mechanism of Acetylcholinesterase Gunnar Schröder (Dipl., 1999/2000): Microscopic Models for Initial Membrane Fusion Berthold Heymann (PhD, 1996–2000): Simulation of Antibody-Antigen Single Molecule Force Microscopy Experiments Chris Brandt (Dipl., 1996/1997): Effective Electrostatic Interactions in Proteins Andreas Briese (Dipl., 1995/1996): Effective Models of Protein Dynamics Berthold Heymann (Dipl., 1995/1996): Enforced Streptavidin-Biotin unbinding Markus Eichinger (Dipl., 1995/1996): A Fast Parallel Multiple Time Step Multipole Algorithm for Molec. Dyn. Simulations Nico Ehrenhofer (Dipl., 1994/1995): Dimensionality of Conformational Protein Dynamics Bernhard Egwolf (Dipl.,1996/1997): Efficient Electrostatics of solvated Proteins

Reports in the Media

G¨ottinger Tageblatt, 22.9.2005: ’Protein in Koralle ist ein ’Lichtschalter’ J. Am. Med. Assoc., 6.10.2004, p.1537: ’Navigating the Body’s Water Channels, Scien- tists Gain Insigts Into Disease’

12 Deutschlandfunk, 16.7.2004 (Kurzinterview Aquaporin und ATPase) Esslinger Zeitung, xxx Discovery Channel Online, 19.3.2003: “Nanotopia” (Interview) Munchner¨ Merkur, 10.4.2002: “Kleister Biomotor der Welt” Göttinger Tageblatt / Hannoversche Allgemeine Zeitung, 5.4.2002: “Wie funktioniert der kleiste Motor der Welt?” Der Tagesspiegel, 20.3.2002: “Wie die Elektromotoren in unseren Zellen arbeiten” FAZ Business-Radio (Berlin), 12.3.2002 (Kurzinterview ATPase) Neues Deutschland, 9.3.2002: “Wie kleinster Bio-Motor arbeitet” ORF Science, 9.3.2002, 16.00h: “Neues ub¨ er den kleinsten Bio-‘Motor’ der Welt” Ludwigsburger Kreiszeitung, 8.3.2002: “Zwei Forscher entschlusseln¨ der Motor des Lebens” Nordwest-Zeitung, 8.3.2002: “Bio-Motor entschlusselt”¨ dpa, 7.3.2002: “Göttinger klären Funktionsweise von kleinstem Bio-Motor auf” Mainpost, 7.3.2002: “Komplizierte Zellstrukturen entschlusselt”¨ NDR-Info, Jan. 2002 (Kurzinterview Aquaporine) Göttinger Tageblatt, 4.1.2002: “Aquaporine: die perfekten Wasserfilter unserer Zellen” Telepolis (Heise Verlag), 28.12.2001: “Wasserfilter der Zelle” Chemical & Engeneering News, 17.12.2001: “Watching Water Line Dance” Eurekalert, 13.12.2001: “Aquaporins — the perfect water filters of the cell” Göttinger Tageblatt, 26.4.2000: “Biegung des Armc¨ hens” Hessisch-Niedersächsische Allgemeine Zeitung, 12.2.2000: “Superhirn simuliert die Welt” Neue Zuricher¨ Zeitung, 31.7.1996: “Bindungskraft von Ligand-Rezeptor-Komplexen” Frankfurter Allgemeine Zeitung, 8.5.1996: “Tauziehen zwischen Molekulen”¨ Suddeutsche¨ Zeitung, 22.2.1996 (report on ligand/receptor-unbinding simulations) Frankfurter Allgemeine Zeitung, 12.10.1994: “Zellmembranen in der Simulation”

Presentations for Schools

Gymnasium Uslar (July 2005) Theodor-Heuss-Gymnasium, Esslingen (June 2004) Felix-Klein-Gymnasium, Göttingen (July 2003) Christian-Rand-Schule, Bad Arolsen (July 2003) Theodor-Heuss-Gymnasium, Göttingen (June 2002) Albert-Einstein-Gymnasium, Hannover (June 2001) Roswitha-Gymnasium, Bad Gandersheim (March 2001) Integrierte Gesamtschule Göttingen (June 2000) Gymnasium ’St. Josef’, Dingelstädt (June 1999)

13 Felix-Klein-Gymnasium, G¨ottingen (June 1999)

14 Letters of Reference

The following persons have agreed to send a letter of reference on request:

Prof. Herman Berendsen Laboratory of Biophysical Chemistry University of Groningen Phone: ++31/5063-4323, -4378 9747 AG Groningen email: [email protected] Niederlande

Prof. Andreas Engel Maurice E. Muller¨ Institute Biocentrum der Universit¨at Basel Phone: ++41/61/2672262 Klingelbergstr 70 email: [email protected] CH-4056 Basel, Schweiz

Prof. Hermann Gaub Ludwig-Maximilians-Universit¨at Munc¨ hen Sektion Physik, LS fur¨ Angewandte Physik Phone: ++49/89/2180-3173, -3172 Amalienstr. 54 email: [email protected] 80799 Munc¨ hen

Prof. Wilfred van Gunsteren ETH Zuric¨ h Physikal. Chemie Phone: ++41/1/632-5501,-5502 ETH Zentrum, CAB email: [email protected] 8092 Zuric¨ h, Schweiz

Prof. Michele Parrinello Swiss Center for Scientiﬁc Computing ETH Zuric¨ h Phone: ++41/91/6108211 Via Cantonale, Galleria 2 email: [email protected] CH-6928 Manno (TI), Schweiz

Prof. Klaus Schulten Beckman Institute 405 North Mathews Av. Phone: ++1/217/244-1604, -2212 Urbana, IL 61801 email: [email protected] U.S.A.

Prof. Jeremy Smith Lehrstuhl fur¨ Biocomputing Universit¨at Heidelberg Phone: ++49/6221/54-8857 69120 Im Neuenheimer Feld 368 email: [email protected] Heidelberg, Germany

Prof. Andrew McCammon Department of Chemistry and Biochemistry University of California at San Diego Phone: ++1/619/534-3575 La Jolla, CA 92093-0365 email: [email protected] U.S.A.

15 Publications in Refereed International Journals

[1] Oliver F. Lange and Helmut Grubmuller.¨ Collective langevin dynamics of conformational motions in proteins. J. Chem. Phys., 124:214903, 2006.

[2] F. J. M. Detmers, B. L. de Groot, E. M. Muller,¨ A. Hinton, I. B. M. Konings, M. Sze, S. L. Flitsch, Helmut Grubmuller,¨ and P. M. T. Deen. Quaternary ammonium compounds as water channel blockers. J. Biol. Chem., 281:14207–14214, 2006.

[3] J. B. Sørensen, K. Wiederhold, E. M. Muller,¨ I. Milosevic, G. Nagy, B. L de Groot, H. Grubmuller,¨ and D. Fasshauer. Sequential N- to C-terminal SNARE complex assembly drives priming and fusion of secretory vesicles. EMBO J., 25:955–966, 2006.

[4] Oliver F. Lange and Helmut Grubmuller.¨ Generalized correlation for biomolecular dynamics. Proteins, 62:1053–1061, 2006.

[5] Gunnar F. Schr¨oder, Ulrike Alexiev, and Helmut Grubmuller.¨ Simulation of ﬂuo- rescence anisotropy experiments: Probing protein dynamics. Biophys. J., 89:3757– 3770, 2005.

[6] Martin Andresen, Markus C. Wahl, Andre C. Stiel, Frauke Gräter, Lars V. Schäfer, Simon Trowitzsch, Gert Weber, Christian Eggeling, Helmut Grubmuller,¨ Stefan W. Hell, and Stefan Jakobs. Structure and mechanism of the reversible photoswitch of a fluorescent protein. Proc. Natl. Acad. Sci. USA, 102:13070–13074, 2005.

[7] Henrike Heise, Sorin Luca, Bert L. de Groot, Helmut Grubmuller,¨ and Marc Baldus. Probing conformational disorder in neurotensin by two-dimensional solid-state NMR and comparison to molecular dynamics simulations. Biophys. J., 89:2113–2120, 2005.

[8] Anna K. Wozniak, Stephanie Nottrott, Eva Kuhn-H¨¨ olsken, Gunnar F. Schr¨oder, Helmut Grubmuller,¨ Reinhard Luhrmann,¨ Claus A. M. Seidel, and Filipp Oesterhelt. Detecting protein-induced folding of the U4 snRNA kink-turn by single-molecule multiparameter FRET measurements. RNA, 11:1545–1554, 2005.

[9] Oliver F. Lange, Helmut Grubmuller,¨ and Bert L. de Groot. Molecular dynamics simulations of protein G challenge NMR-derived correlated backbone motions. Angew. Chem. Int. Ed., 44:3394–3399, 2005.

[10] Frauke Gr¨ater, Jianhua Shen, Hualiang Jiang, Mathias Gautel, and Helmut Grubmuller.¨ Mechanically induced titin kinase activation studied by force probe molecular dynamics simulations. Biophys. J., 88:790–804, 2005.

[11] A. de Meijere, H. Schill, S. I. Kozhushkov, R. Walsh, E. M. Muller,¨ and H. Grubmuller.¨ Cyclopropylidenes, bicyclopropylidenes, and vinylcarbenes — some modes of formation and preparative applications. Russ. Chem. Bull. (Intl. Ed.), 53:947–959, 2004.

16 [12] S. Jeney, E. H. K. Stelzer, H. Grubmuller,¨ and E.-L. Florin. Mechanical properties of single motor molecules studied by three-dimensional thermal force probing in optical tweezers. Chem. Phys. Chem., 5:1150–1158, 2004.

[13] Thomas Pöhlmann, Rainer A. Böckmann, Helmut Grubmuller,¨ Barbara Uchanska- Ziegler, Andreas Ziegler, and Ulrike Alexiev. Differential peptide dynamics is linked to major histocompatibility complex polymorphism. J. Biol. Chem., 279:28197– 28201, 2004.

[14] Gunnar F. Schr¨oder and Helmut Grubmuller.¨ FRETsg: Biomolecular structure model building from multiple FRET experiments. Computer Phys. Comm., 158:150–157, 2004.

[15] Rainer B¨ockmann and Helmut Grubmuller.¨ Multistep binding of divalent cations to phospholipid bilayers: A molecular dynamics study. Angew. Chem. Int. Ed., 43:1021–1024, 2004.

[16] M. Margittai, J. Widengren, E. Schweinberger, G. F. Schröder, D. Fasshauer, S. Felekyan, E. Haustein, M. König, H. Grubmuller,¨ R. Jahn, and C. A. M. Seidel. Single-molecule fluorescence resonance energy transfer reveals a dynamic equilibrium between closed and open conformations of syntaxin 1. Proc. Natl. Acad. Sci. USA, 4:561–602, 2003.

[17] Gunnar F. Schr¨oder and Helmut Grubmuller.¨ Maximum likelihood trajectories from single molecule ﬂuorescence resonance energy transfer experiments. J. Chem. Phys., 119:9920–9924, 2003.

[18] Bert L. de Groot, Tomaso Frigato, Volkhard Helms, and Helmut Grubmuller.¨ The mechanism of proton exclusion in the aquaporin-1 water channel. J. Molec. Biol., 333:279–293, 2003.

[19] Rainer A. B¨ockmann and Helmut Grubmuller.¨ Conformational dynamics of the F1- ATPase β-subunit: A molecular dynamics study. Biophys. J., 85:1482–1491, 2003.

[20] Rainer A. B¨ockmann, Agnieszka Hac, Thomas Heimburg, and Helmut Grubmuller.¨ Eﬀect of sodium chloride on a lipid bilayer. Biophys. J., 85:1647–1655, 2003.

[21] Volker Knecht and Helmut Grubmuller.¨ Mechanical coupling via the membrane fusion SNARE protein syntaxin-1A: A molecular dynamics study. Biophys. J., 84:1527–1547, 2003.

[22] Bert L. de Groot, Andreas Engel, and Helmut Grubmuller.¨ The structure of the Aquaporin-1 water channel: a comparison between cryo-electron microscopy and x- ray crystallography. J. Molec. Biol., 325:485–493, 2003.

[23] P. J. L. Werten, H. W. R´emigy, B. L. de Groot, D. Fotiadis, A. Philippsen, H. Stahlberg, H. Grubmuller,¨ and A. Engel. Progress in the analysis of membrane protein structure and function. FEBS Lett., 529:65–72, 2002.

17 [24] Bert L. de Groot, D. Peter Tieleman, Peter Pohl, and Helmut Grubmuller.¨ Water permeation through gramicidin A: desformylation and the double helix; a molecular dynamics study. Biophys. J., 82:2934–2942, 2002.

[25] Rainer B¨ockmann and Helmut Grubmuller.¨ Nanoseconds molecular dynamics simulation of primary mechanical energy transfer steps in F1-ATP synthase. Nature Struct. Biol., 9:198–202, 2002.

[26] E. Matthias Muller,¨ Armin de Meijere, and Helmut Grubmuller.¨ Predicting unimolecular chemical reactions: Chemical ﬂooding. J. Chem. Phys., 116:897–905, 2002.

[27] Bert L. de Groot and Helmut Grubmuller.¨ Water permeation across biological membranes: Mechanism and dynamics of aquaporin-1 and GlpF. Science, 294:2353–2357, 2001.

[28] B. L. de Groot, A. Engel, and H. Grubmuller.¨ A reﬁned structure of human Aqua- porin 1. FEBS Lett., 504:206–211, 2001.

[29] Berthold Heymann and Helmut Grubmuller.¨ Molecular dynamics force probe simulations of antibody/antigen unbinding: Entropic control and non-additivity of unbinding forces. Biophys. J., 81:1295–1313, 2001.

[30] Bert L. de Groot, Xavier Daura, Alan E. Mark, and Helmut Grubmuller.¨ Essen- tial dynamics of reversible peptide folding: Memory-free conformational dynamics governed by internal hydrogen bonds. J. Molec. Biol., 309:299–313, 2001.

[31] Rainer Ossig, Hans Dieter Schmitt, Bert de Groot, Dietmar Riedel, Sirkka Ker¨anen, Hans Ronne, Helmut Grubmuller,¨ and Reinhard Jahn. Exocytosis requires asymme- try in the central layer of the SNARE complex. EMBO J., 19:6000–6010, 2000.

[32] Brita G. Schulze, Helmut Grubmuller,¨ and Jeﬀrey D. Evanseck. Functional signif- icance of hierarchical tiers in carbonmonoxy myoglobin: Conformational substates and transitions studied by conformational ﬂooding simulations. J. Am. Chem. Soc., 122:8700–8711, 2000.

[33] Bert L. de Groot, J. Bernard Heymann, Andreas Engel, Kaoru Mitsuoka, Yoshinori Fujiyoshi, and Helmut Grubmuller.¨ The fold of human Aquaporin 1. J. Molec. Biol., 300:987–994, 2000.

[34] Berthold Heymann and Helmut Grubmuller.¨ Dynamic force spectroscopy of molecular adhesion bonds. Phys. Rev. Lett., 84:6126–6129, 2000.

[35] Berthold Heymann and Helmut Grubmuller.¨ Elastic properties of poly(ethylene- glycol) studied by molecular dynamics stretching simulations. Chem. Phys. Lett., 307:425–432, 1999.

[36] Berthold Heymann and Helmut Grubmuller.¨ ’Chair-boat’ transitions and side groups aﬀect the stiﬀness of polysaccharides. Chem. Phys. Lett., 305:202–208, 1999.

18 [37] Berthold Heymann and Helmut Grubmuller.¨ AN02/DNP-hapten unbinding forces studied by molecular dynamics atomic force microscopy simulations. Chem. Phys. Lett., 303:1–9, 1999. [38] Helmut Grubmuller¨ and Paul Tavan. Multiple time step algorithms for molecular dynamics simulations of proteins: How good are they? J. Comp. Chem., 19:1534– 1552, 1998. [39] Markus Eichinger, Helmut Grubmuller,¨ Helmut Heller, and Paul Tavan. FA- MUSAMM: An algorithm for rapid evaluation of electrostatic interactions in molecular dynamics simulations. J. Comp. Chem., 18:1729–1749, 1997. [40] Helmut Grubmuller,¨ Berthold Heymann, and Paul Tavan. Ligand binding: Molecular mechanics calculation of the streptavidin-biotin rupture force. Science, 271:997–999, 1996. [41] Helmut Grubmuller.¨ Predicting slow structural transitions in macromolecular systems: Conformational Flooding. Phys. Rev. E, 52:2893, 1995. [42] Helmut Grubmuller¨ and Paul Tavan. Molecular dynamics of conformational substates for a simplified protein model. J. Chem. Phys., 101:5047–5057, 1994. [43] Helmut Grubmuller,¨ Helmut Heller, Andreas Windemuth, and Klaus Schulten. Gen- eralized Verlet algorithm for efficient molecular dynamics simulations with long-range interactions. Molec. Sim., 6:121–142, 1991. [44] Paul Tavan, Helmut Grubmuller,¨ and Hans Kuhnel.¨ Self-organization of associative memory and pattern classification: Recurrent signal processing on topological feature maps. Biolog. Cybern., 64(2):95–105, 1990. [45] Helmut Heller, Helmut Grubmuller,¨ and Klaus Schulten. Molecular dynamics simulation on a parallel computer. Molec. Sim., 5:133–165, 1990.

Reviews, Book Chapters, and other Publications

[46] Bert L. de Groot, Rainer A. Böckmann, and Helmut Grubmuller.¨ Proteindynamik- Simulationen. Molekulare Nanomaschinen unter der Lupe. Physik in unserer Zeit, 37:73–79, 2006. [47] Helmut Grubmuller,¨ Stefan Seeger, and Harald Tschesche. Aufbau, Funktion und Diagnostik biogener Molekule.¨ In: Bergmann/Schaefer, Lehrbuch der Experimental- physik, Band 5: Gase, Nanosysteme, Flussigk¨ eiten, pp. 977–1067, Karl Kleinermanns (Hrsg.), de Gruyter, Berlin, 2006. [48] Martin Andresen, Markus C. Wahl, André C. Stiel, Frauke Gräter, Lars V. Schäfer, Simon Trowitzsch, Gert Weber, Christian Eggeling, Helmut Grubmuller,¨ Stefan W. Hell, and Stefan Jakobs. Insight into the structure and mechanism of the reversible photoswitch of a fluorescent protein. MPIbpc News 12, Max-Planck-Institut fur¨ biophysikalische Chemie, Göttingen, 2005.

19 [49] Bert L. de Groot and Helmut Grubmuller.¨ The dynamics and energetics of water permeation and proton exclusion in aquaporins. Curr. Opin. Struct. Biol., 15:176– 183, 2005.

[50] B. L. de Groot and H. Grubmuller.¨ Aquaporine: Die perfekten Wasserﬁlter der Zelle. BIOspektrum, 4:384–386, 2004.

[51] Helmut Grubmuller.¨ Force probe molecular dynamics simulations. In Ulrich Nien- haus, editor, Protein–Ligand Interactions, pages 493–515, Totowa, NJ, USA, 2005. The Humana Press Inc.

[52] Helmut Grubmuller.¨ Proteins as molecular machines: Force probe simulations. In Norbert Attig, Kurt Binder, Helmut Grubmuller,¨ and Kurt Kremer, editors, Com- putational Soft Matter: From Synthetic Polymers to Proteins, pages 401– 421, Julic¨ h, 2004. Forschungszentrum Julic¨ h.

[53] Helmut Grubmuller.¨ What happens if the room at the bottom runs out? A close look at small water pores. Proc. Natl. Acad. Sci. USA, 100:7421–7422, 2003.

[54] Yoshinori Fujiyoshi, Kaoru Mitsuoka, Bert L. de Groot, Ansgar Philippsen, Helmut Grubmuller,¨ Peter Agre, and Andreas Engel. Structure and function of water channels. Curr. Opin. Struct. Biol., 12:509–515, 2002.

[55] Reinhard Jahn and Helmut Grubmuller.¨ Membrane fusion. Curr. Opin. Cell Biol., 14:488–495, 2002.

[56] Bert L. de Groot and Helmut Grubmuller.¨ Aquaporine — Wasserﬁlter der Zelle. BIOforum, 6:387–389, 2002.

[57] Helmut Grubmuller.¨ Mechanik molekularer “Maschinen” am Beispiel des Aquaporins und der F1-ATPase. Jahrbuch 2002 der Max-Planck-Gesellschaft, S. 121–125 (2002).

[58] Gunnar Schr¨oder and Helmut Grubmuller.¨ FretTrace: Create maximum likelihood trajectories from single molecule FRET data, 2002. (electronic publication, http://- www.mpibpc.gwdg.de/abteilungen/071/frettrace/index.html.

[59] Rainer A. B¨ockmann and Helmut Grubmuller.¨ Wie funktioniert der kleinste Mo- tor der Welt? MPIbpc News 7, Max-Planck-Institut fur¨ biophysikalische Chemie, G¨ottingen, 2002.

[60] Gunnar Schr¨oder and Helmut Grubmuller.¨ FRETsg: A FRET structure generator, 2002. (electronic publication, http://www.mpibpc.gwdg.de/abteilungen/071/fretsg- 1.0/fretsg.html.

[61] Matthias Rief and Helmut Grubmuller.¨ Force spectroscopy of single biomolecules. Chem. Phys. Chem., 3:255–261, 2002.

[62] Bert L. de Groot and Helmut Grubmuller.¨ Aquaporine — Die perfekten Wasser- ﬁlter der Zelle. MPIbpc News 3, Max-Planck-Institut fur¨ biophysikalische Chemie, G¨ottingen, 2002.

20 [63] Rainer B¨ockmann and Helmut Grubmuller.¨ Der kleinste Motor der Welt. Wechsel- wirkung, 3(115):42–44, 2002.

[64] Bert de Groot and Helmut Grubmuller.¨ Proteine als Filter reinsten Wassers. Max Planck Forschung, 1:8–9, 2002.

[65] Matthias Rief and Helmut Grubmuller.¨ Kraftspektroskopie von einzelnen Biomolekulen.¨ Physikalische Bl¨atter, pages 55–61, Feb. 2001.

[66] Markus Eichinger, Helmut Heller, and Helmut Grubmuller.¨ EGO – An eﬃcient molecular dynamics program and its application to protein dynamics simulations. In Rudiger¨ Esser, Peter Grassberger, Johannes Grotendorst, and Marius Lewerenz, editors, Workshop on Molecular Dynamics on Parallel Computers, John von Neumann Institute for Computing (NIC) Research Centre Julic¨ h, Germany, 8–10 February 1999, pages 154–174, Singapore 912805, 2000. World Scientiﬁc.

[67] K. Moﬀat, J.-P. Changeux, D. M. Crothers, H. Grubmuller,¨ G. U. Nienhaus, M. U. Palma, F. G. Parak, K. Schulten, and A. Warshel. How does complexity lead to apparently simple function? In H. Frauenfelder, J. Deisenhofer, and P. Wolynes, editors, Simplicity and Complexity in Proteins and Nucleic Acids, Dahlem Workshop Reports, pages 255–280, Berlin, 1999. Dahlem University Press.

[68] Helmut Grubmuller¨ and Berthold Heymann. Proteindynamik von Ligand/Rezeptor- Bindungen. MPIbpc News 1, Max-Planck-Institut fur¨ biophysikalische Chemie, G¨ottingen, 1999.

[69] Markus Eichinger, Berthold Heymann, Helmut Heller, Helmut Grubmuller,¨ and Paul Tavan. Conformational dynamics simulations of proteins. In P. Deuﬂhard, J. Her- mans, B. Leimkuhler, A. E. Mark, S. Reich, and R. D. Skeel, editors, Lecture Notes in Computational Science and Engineering (Vol 4). Computational Molec- ular Dynamics: Challenges, Methods, Ideas, pages 78–97. Springer, 1998.

[70] Berthold Heymann and Helmut Grubmuller.¨ Einzelmolekul-Kraftmikrosk¨ opie- Simulationen an Antik¨orper/Antigen-Komplexen. User report, John von Neumann- Institut fur¨ Computing, Forschungszentrum Julic¨ h, 52425 Julic¨ h, 1998.

[71] Helmut Grubmuller¨ and Berthold Heymann. Computing binding forces with molecular mechanics. In Christian Colliex, Andreas Engel, and Jean Fourmentin-Guilbert, editors, Proceedings of the Workshop ‘STM – AFM – SNOM: New Nan- otools for Molecular Biology’, Fondation Fourmentin-Guilbert, 93160 Noisy Le Grand (France), 1997. Issue report.

[72] Helmut Grubmuller¨ and Berthold Heymann. Microscopic interpretation of AFM single molecule rupture experiments by molecular dynamics simulations. In Christian Colliex, Andreas Engel, and Jean Fourmentin-Guilbert, editors, Proceedings of the Workshop ‘STM – AFM – SNOM: New Nanotools for Molecular Biology’, April 16th–18th, 1997, pages III 45–50, Fondation Fourmentin-Guilbert, 93160 Noisy Le Grand (France), 1997.

21 [73] Matthias Rief, Filipp Oesterhelt, Helmut Grubmuller,¨ and Hermann Gaub. Kraftmessungen an einzelnen Molekulen.¨ Einsichten — Forschung an der Ludwig–Maximilians–Universit¨at Munc¨ hen, 1:21–23, 1997.

[74] Helmut Grubmuller,¨ Berthold Heymann, and Paul Tavan. Simulation eines moleku- laren Erkennungsvorgangs. Spektrum der Wissenschaft, S. 14–16, M¨arz 1997.

[75] Helmut Grubmuller.¨ Solvate: A program to create atomic solvent models, 1996. (electronic publication, http://www.mpibpc.gwdg.de/abteilungen/071/solvate.html).

[76] Markus Eichinger, Helmut Grubmuller,¨ Helmut Heller, and Paul Tavan. Fast molecular dynamics simulation on a Parsytec PowerXplorer system. User report, Heinrich- Heine-Universität, Universitätsrechenzentrum / Parsytec Computer GmbH, Univer- sitätsstr., 40225 Dusseldorf,¨ Germany, June 1995.

[77] Markus Eichinger, Helmut Grubmuller,¨ and Helmut Heller. User Manual for EGO VIII, Release 2.0. Theoretische Biophysik, Institut fur¨ Medizinische Optik, Universit¨at Munc¨ hen, Theresienstr. 37, 80333 Munc¨ hen, Germany (1995); electronic access: http://www.imo.physik.uni-muenchen.de/ego.html.

[78] H. Grubmuller,¨ N. Ehrenhofer, and P. Tavan. Conformational dynamics of proteins: Beyond the nanosecond time scale. In M. Peyard, editor, Proceedings of the Workshop ‘Nonlinear Excitations in Biomolecules’, May 30–June 4, 1994, Les Houches (France), pages 231–240. Centre de Physique des Houches (France), Springer-Verlag, 1995.

[79] Helmut Grubmuller.¨ Proteine: Einblicke in ihre Funktionsweise. ‘Spektrum Videothek’, Sept. 1994. Spektrum akademischer Verlag (scientiﬁc american), Hei- delberg (Germany).

[80] Helmut Grubmuller.¨ On the suitability of eﬃcient many-body algorithms for molecular dynamics simulations of biological macromolecules. In K. I. M. McKinnon and F. Plab, editors, Proceedings of the Second Parallel Numerical Analysis Workshop, June 25–26, 1992, Edinburgh, UK, pages 226–238. Edinburgh Par- allel Computing Centre, University of Edinburgh, 1992.

[81] Helmut Grubmuller,¨ Klaus D¨ohring, Paul Tavan, Marco Nonella, and Dieter Oester- helt. BR AT WORK: A computeranimation for the 13-14-cis-model of the photochemical cycle of bacteriorhodopsin. J. Mol. Graphics, 11(4):258, 1993.

[82] P. Tavan and H. Grubmuller.¨ Selbstorganisation von Assoziativspeichern und Musterklassiﬁkatoren: Rekurrente Signalverarbeitung auf topologischen Merkmal- skarten. In Kleinheubacher Berichte, Bd. 34, pages 573–582, Forschungsinstitut beim FTZ, Darmstadt, 1991. DBP Telekom.

[83] Klaus Boehncke, Helmut Heller, Helmut Grubmuller,¨ and Klaus Schulten. Molec- ular dynamics simulations on a systolic ring of transputers. In Alan S. Wagner, editor, Transputer Research and Applications 3, pages 83–94. North American Transputer Users Group, IOS Press, Van Diemenstraat 94, 1013 CN Amsterdam,

22 The Netherlands, 1990. Proceedings of the Third Conference of the North American Transputer Users Group, April 26–27, 1990 — Sunnyvale, CA.

[84] Helmut Grubmuller,¨ Helmut Heller, and Klaus Schulten. Eine CRAY fur¨ ’jedermann’. mc, pages 48–65, November 1988.

Patents

[85] P. M. T. Deen, F. J. M. Detmers, S. Hohmann, S. Nielsen, J. Frøkiær, A. Engel, P. J. L. Werten, H. Grubmuller,¨ B. L. de Groot, E. M. Muller,¨ S. L. Flitsch, and F. K. Brown (inventors). Use of quaternary ammonium compounds as speciﬁc blockers of transport through aquaporin, compositions comprising the compounds and method of selecting the compounds. (Patent Nr. PCT/EP04/003629, deposited 31- 3-2004).

Theses

[86] Helmut Grubmuller.¨ Theorie und Simulation induzierter Konformationsdynamik von Proteinen. Habilitationsschrift, Georg-August-Universit¨at G¨ottingen, Germany, Juli 2001.

[87] Helmut Grubmuller.¨ Molekulardynamik von Proteinen auf langen Zeitskalen. PhD thesis, Technische Universit¨at Munc¨ hen, Germany, 1994.

[88] Helmut Grubmuller.¨ Dynamiksimulation sehr großer Makromolekule¨ auf einem Par- allelrechner. Diploma thesis, Technische Universit¨at Munc¨ hen, 1989.

23 Invited Talks at Conferences and Workshops

1. ICN+T 2006, Basel, Switzerland, July 31–Aug. 3 (2006): Molecular dynamics simulations of biological nanomachines: May the force be with you

2. CENS-Seminar, Univ. Munich, Prof. Vivie-Riedle, June 2nd (2006): Proteins as Complex Nanomachines: Molecular dynamics simulations reveal Nature’s Tricks

3. WE-Heraeus-Seminar: Biomolecular Simulation: From Physical Principles to Bio- logical Function, Bad Honnef, May 22–24 (2006): Proteins as complex machines: nature’s nanotechnology benchmarks

4. Lecturer at EMBO Course on Proteins: structure, dynamics, energetics, MPG-CAS Partner Institute for Computational Biology, Shnaghai (Cina) May 10–17 (2006): Force probe molecular dynamics simulations: Principle and applications

5. Sitzung der Nordrhein-Westf¨ahlischen Akademie der Wissenschaften, Dusseldorf,¨ Apr. 7–8 (2006): Protein als biologische Nanomaschinen: Computersimulationen helfen, sie zu begreifen

6. 41. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 14–17 (2006): Proteins: No water — no function

7. Academie Royale Symposium: Single molecules, what can we learn?, Brussels, Dec. 16 (2005): Mechanically induced titin kinase activation studied by force probe molecular dynamics simulations

8. M2CELL Fourmentin-Guilbert-Workshop, Fontevraud, Dec. 3–6 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

9. Section Symposium of the BMS of the Max-Planck-Society, Berlin, Nov. 22–25 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

10. 87th International Bunsen Meeting ’Mechanically induced chemistry — Theory and experiment’, Tutzing, Oct. 3–6 (2005): Mechanism of the reversibly photoswitching ﬂuorescent protein asFP595

11. 90th International Bunsen Meeting ’Time-resolved transformations in complex molecular environments: Pushing the frontiers in experiment and theory’, G¨ottingen, Sept. 26–28 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

12. Congress ’Physics of Life’ (Satellite Congress to the International Biophysics Congress), Bordeaux, France, Sept. 2–3 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

13. International Biophysics Congress 2005, Montpellier, France, Aug. 27 – Sept. 1 (2005): Mechanically induced titin kinase activation studied by force probe molecular dynamics simulations

24 14. International workshop ’Physics of Life’, Krogerup, Denmark, Aug. 21–27 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

15. Summer School ’Biosensing with channels’, IUB Bremen, Germany, July 30 – Aug. 4 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

16. Nobel Symposium 131: Controlled Nanoscale Motion in Biological and Artiﬁcial Systems, B¨ackaskog Slott, Sweden, June 13–17 (2005): Mechanically induced titin kinase activation studied by force probe molecular dynamics simulations (invited poster contribution)

17. International Workshop on Classical and Quantum Dynamical Simulations in Chem- ical and Biological Physics, Dresden, June 6–11 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

18. Joint meeting of Swiss and German Biophysicist, Hunfeld,¨ May 5–7 (2005): Me- chanically induced titin kinase activation studied by force probe molecular dynamics simulations

19. Faltertage 2005, Prof. J¨ahnicke Wittenberg, Apr. 8–9 (2005): Mechanically induced titin kinase activation studied by force probe molecular dynamics simulations

20. 1st Joint German/British Bioenergetics Conference ’Mechanisms of Bioenergetic Membrane Proteins: Structures and Beyond’, Wiesbaden, Mar. 20–23 (2005): Elab- orate pores and complex machines: nature’s nanotechnology benchmarks

21. The Fritz Haber Symposium on Biophysical Dynamics, Jerusalem, Mar. 13–15 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

22. Workshop ’Single Molecule Techniques in Biophysics and Drug Discovery’, Linz, Feb. 4–7 (2005): Mechanically induced titin kinase activation studied by force probe molecular dynamics simulations

23. Workshop ’Frontiers in Unimolecular Reaction Dynamics and Kinetics’, G¨ottingen, Dec. 13–15 (2004): Thermal Rearrangement/Fragmentation of [3]Rotane and Re- lated Compounds

24. Workshop ’Formation and Stability of Beta Sheets’, Berlin, Oct. 14–16 (2004): Me- chanically induced titin kinase activation studied by force probe molecular dynamics simulations

25. International Conference on High Resolution Site Selective Spectroscopy, Bayreuth, Germany, July 15–18 (2004): Towards an Atomistic Simulation of Single Molecule Spectroscopy

26. Third German-American Symposium ’Frontiers of Chemistry – Horizonte der Chemie’, Kloster Seeon, Germany, July 15–18 (2004): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

25 27. 3rd Symposium on Micro- and Nanostructures of Biological Systems, Martin Luther University Halle-Wittenberg, Halle, Germany, June 7–8 (2004): Protein Dynamics Simulations: Grasping Molecular Nanomachines

28. ESF-Workshop ’Statistical Physics of Molecular and Cell Biological Systems and Networks’, Heidelberg, April 1–2 (2004): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

29. John von Neumann Winter School ’Computational Soft Matter: From Synthetic Polymers to Proteins’, Gustav-Stresemann-Institute, Bonn, Germany, March 4–5 (2004): Proteins as Molecular Machines: Force Probe Simulations

30. DPG spring meeting, Munc¨ hen, Mar. 22-26 (2004): Molecular dynamics simulation of single molecule force probe experiments

31. Annual meeting of the Americal Physical Society, Montreal, Mar. 22-26 (2004): Elucidating the mechanism of protein water channels by molecular dynamics simulations

32. Optical Spectroscopy of Biomolecular Dynamics, Kloster Banz, Staﬀelstein, Mar. 21-22 (2004): Protein Dynamics Simulations: Grasping Molecular Nanomachines

33. Basel Computational Biology Conference, Basel, Mar. 18–20 (2004): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

34. DPG spring meeting, Regensburg, Mar. 10–11 (2004): Aquaporin Proteins: Perfect Filters

35. Gordon Conference ’Ligand Recognition’, Venture, USA, Feb. 29 – Mar. 4 (2004): Molecular mechanisms of aquaporins and F1 ATP synthase studied by protein dynamics simulations

36. DFG-Symposium to initiate priority area ’Biomolecular Simulation’, Bonn, Jan. 28 (2004): Biomolecular Simulations: Status and Perspectives

37. DFG-Symposium to initiate priority area ’Spectroscopic subnanometer distance measurements’, K¨onigstein (Taunus), Jan. 16–17 (2004): Simulating single molecule experiments

38. Conference ’Understanding Structure-Function Relationships in Membrane Integral Receptors’, Berlin, Dec. 4–5 (2003) Function from Structure: Aquaporins and F1- ATP Synthase

39. CECAM Meeting ’Self-Organization in (Bio)Molecular Systems’, Oct. 20–22 (2003), Lyon (France): Ion-Bilayer Interactions

40. GDCh annual meeting, Munich, Oct. 6–10 (2003): Simulationen molekularer Nanomaschinen

41. CECAM Meeting ’Finding reaction paths in complex systems’, Sept. 28–30 (2003), Paris (France): Predicting conformational and chemical transitions: Flooding

26 42. Telluride Research Academy Protein Dynamics Workshop, Telluride (Colorado), July 14–18 (2003): Protein Dynamics Simulations: Grasping Molecular Nanoma- chines

43. 12th European Carbohydrate Symposium, Grenoble (France), July 6–11 (2003): Me- chanical Properties and Conformational Dynamics of Polysaccharides

44. Joint Meeting of Belgian and German Biophysicists: ’Folding, Dynamics and Inter- action of Biomolecules’, Hunfeld,¨ May 29–June 1 (2003): Protein Dynamics Simu- lations: Grasping Molecular Nanomachines

45. 17. Molecular Modelling Workshop, Erlangen, May 28 (2003): Function from Struc- ture: Aquaporins and F1-ATP Synthase

46. International Workshop on biology and physics at interfaces, Julic¨ h, May 21–23 (2003): Protein Dynamics Simulations: Grasping Molecular Nanomachines

47. International Symposium of the VW-Foundation, Conformational Control of Biomolecular Function, Schloß Velen, West-Munsterland,¨ Germany, May 7–9 (2003): Mechanical Coupling via the Membrane Fusion SNARE Protein Syntaxin 1A

48. Idea-Finding Symposium for the Frankfurt Institute for Advanced Studies, Frank- furt, April 15–17 (2003): Protein Dynamics: A challenge for Theoreticians

49. 225th Americal Chemical Society National Meeting, New Orleans, March 23–27 (2003): Nanoseconds Molecular Dyanmics Simulation of Primary Mechanical En- ergy Transfer Steps in F1-ATP Synthase

50. Eigth International Symposium on Simulation Science, Hayama, Tokyo (Japan), March 5–7 (2003): Protein Dynamics Simulations: Grasping Molecular Nanoma- chines

51. WE-Heraeus-Seminar: Biological Physics of Proteins — Structure, Flexibility and Function, Bad Honnef, Feb. 9–12 (2003): Protein Dynamics Simulations: Grasping Molecular Nanomachines

52. Challenges in Biophysics, Faculty of Physics and Astronomy, Heidelberg Univer- sity, Feb. 6–7 (2003): Protein Dynamics Simulations: Grasping Molecular Nano- Machines

53. V. Annual Linz Winter Workshop on Single Molecule Techniques, Linz/Austria, Jan. 31–Feb. 3 (2003): Protein Dynamics Simulations: Grasping Molecular Nano- Machines

54. 16. GDCh/CIC Workshop ’Software-Entwicklung in der Chemie’, Kleinmach- now/Berlin, Nov. 10–12 (2002): Protein Dynamics Simulations: Grasping Molecular Nano-Machines

55. WE-Heraeus-Seminar 282 ’Single Molecule Dynamics’, Bad Honnef, June 18–21 (2002): Protein Dynamics Simulations: Grasping Molecular Nano-Machines

27 56. Biophysik Workshop der Universit¨at Heidelberg, Kai Schwenzer, Oberﬂockenbach, Mar. 4–8 (2002): Frontiers in Biophysics (four lectures)

57. Modern Trends in Computational Physics, Basel, Feb. 25–26 (2002): Molecular Dynamics Force Probe Simulations of Protein Function

58. ESS International Conference on Flexibility and Function of Proteins, Heidelberg, Jan. 25–27 (2002): Bridging the gap between theory and experiment

59. Europhysics Conference on Computational Physics, Aachen, Germany, Sept. 5–8 (2001): Protein Dynamics Simulations: Grasping Molecular Nano-Machines

60. International Symposium of the VW-Foundation, Insolated Molecules of Biological Interest, Schloß Mickeln, Dusseldorf,¨ Germany, June 27–July 1 (2001): Molecular Dynamics Force Probe Simulations: Grasping Molecular Nano-Machines

61. Bunsentagung 2001, Stuttgart (Germany) May 24–26 (2001): Force Probe Simula- tions and Conformational Motions of Proteins (plenary lecture)

62. DFG-Symposium ’Molecular Mechanisms of Prion-Replication and -Pathogenesis’, Bonn (Germany), April 27 (2001): Conformational Flexibility of Prion Protein Frag- ment 121–231

63. DPG-Schule fur¨ Physik: Computational Physics, Bad Honnef (Germany) April 2–6 (2001): Protein Dynamics Simulations: Grasping Molecular Nano-Machines

64. International Conference on the Structure, Dynamics and Function of Proteins in Biological Membranes, Monte Verita, March 13–17 (2001): Molecular Dynamics Force Probe Simulations

65. Kolloquium fur¨ Bioinformatik, Forschungszentrum Julic¨ h (Germany), Dec. 15–16 (2000): Proteindynamiksimulationen: Molekulare ’Nano-Maschinen’ unter der Lupe

66. Symposium ’Science with membranes — Science with limits’, Ringberg (Germany), Nov. 10–11 (2000): Molecular Force Probe Simulations

67. Graduate Retreat of the Max-Planck Institute for Biochemistry, Ringberg (Ger- many), Oct. 25–27 (2000): Konformationelle Plastizit¨at von Proteinen: Molekulare ’Nano-Maschinen’ unter der Lupe

68. Lecturer at EMBO Course on Biomolecular Simulation, EMBL, Heidelberg (Ger- many) July 5–13 (2000): (1) Force probe molecular dynamics simulations; (2) Molec- ular dynamics and essential dynamics

69. International Workshop on Numerical Solutions of Polymer and Cell Dynamics, Bad Honnef (Germany), June 13–16 (2000): Force Probe Simulations and Confor- mational Motions of Proteins

70. Third German-American Frontiers of Engineering Symposium, Bremen (Germany), Apr. 12–15 (2000): Protein Dynamics Simulations: Grasping Molecular Nano- Machines (plenary lecture)

28 71. Computational Science Workshop 2000, Tsukuba (Japan), Mar. 13–15 (2000): Pro- tein Dynamics Simulations: Grasping Molecular Nano-Machines (plenary lecture) 72. Festveranstaltung zur Einweihung des neuen Parallelrechners IBM RS/6000 SP, GWDG Göttingen, Feb. 10 (2000): Proteindynamiksimulation: Eine Heraus- forderung fur¨ schnelle Rechner (plenary lecture) 73. CECAM Workshop on Modelling Concerted Motions in Biomolecules, Lyon, France, Oct. 11–14 (1999): Conformational Flooding Studies of the Prion Protein 74. Jahrestagung der Deutschen Biophysikalischen Gesellschaft, University of Ulm, Ger- many, Oct. 3–6 (1999): Konformationelle Plastizität von Proteinen und deren Funk- tion (plenary lecture) 75. Symposium ’New Trends in Physics, Chemistry, and Biology with Single Molecules’, Wiesbaden, Germany, July 14–16 (1999): Molecular Dynamics Simulation of Single Molecule AFM Experiments 76. Workshop ’Opportunities in Molecular Biomedicine in the Era of Petaflop Comput- ing’, NIH, Rockville, U.S.A, Mar. 3–4 (1999): Conformational Dynamics of Pro- teins: Watching Nanomachines at Work 77. Workshop ‘Molecular Dynamics an Parallel Computers’, Julic¨ h, Feb. 8–10 (1999): EGO – An Efficient Molecular Dynamics Program and Protein Dynamics Applica- tions 78. Car-Parrinello Molecular Dynamics 99, Schloß Ringberg, Jan. 18–22 (1999): Pre- dicting Reaction Pathways 79. 83rd Dahlem Workshop on Simplicity and Complexity in Proteins and Nucleic Acids, Berlin, May 17–22 (1998) 80. Symposium in Computational Sciences: ’Bioinformatics: From Experiment to Bio- logical Knowledge’, Biozentrum, University of Basel, Dec. 11–12 (1997): Dynamic simulation of large systems: closing the gap between experiment and model 81. Second International Symposium on Algorithms for Macromolecular Modelling, Konrad-Zuse-Zentrum fur¨ Informationstechnik, Berlin, May 21–24 (1997): Con- formational Dynamics Simulations of Proteins 82. Workshop STM–AFM–SNOM: New Nanotools for Molecular Biology, Fourmentin- Guilbert Scientific Foundation, Abbey of Royaumont (France), Apr. 16–18 (1997): Computing Binding Forces with Molecular Mechanics 83. 5. Colloquium of the DFG-Schwerpunkt ‘Neue mikroskopische Techniken fur¨ Bi- ologie und Medizin’, Rostock, Mar. 4–6 (1997): Mikroskopische Interpretation von AFM-Einzelmolekulexp¨ erimenten: Der Mechanismus des Schlussel-Schloß-Prinzips¨ 84. Annual Biophysics Conference 1996 of the German Biophysical Society, Leipzig, Sept. 18–21 (1996): Molekular Dynamics Simulation of Proteins: Methods, Appli- cations, Perspectives (plenary lecture)

29 85. 4. Colloquium of the DFG-Schwerpunkt ‘Neue mikroskopische Techniken fur¨ Biolo- gie und Medizin’, Gunzburg,¨ May 13–15 (1996): Molekulardynamik-Simulationen zur Vorhersage und Interpretation von AFM-experimentell bestimmten Ligand- Rezeptor-Bindungskr¨aften

86. Spring meeting of the Sektion Membranen/Zellen/Netzwerke der Deutschen Gesellschaft fur¨ Biophysik, Gomadingen, Mar. 20–22 (1996): Computersim- ulation von Kraftmikroskopieexperimenten: Vorhersage von Ligand-Rezeptor- Bindungskr¨aften

87. The 1st Munich Workshop on Proteins at Soft Surfaces, Munich, Mar. 18/19 (1996): Molecular dynamics simulation of a protein–ligand unbinding process

88. 150. WE-Heraeus-Seminar 1995, Bad Honnef, Dec. 11–14 (1995): Predicting Slow (µs) Conformational Motions in Proteins: Conformational Flooding (invited poster)

89. Annual Meeting of the Deutsche Gesellschaft fur¨ Biophysik 1995, Wurzburg,¨ Sept. 24–27 (1995): Ein atomares Modell der Streptavidin-Biotin Bindung

90. 6. Workshop ‘Spectroscopy of Photoreceptors’ Schloß Ringberg, Oct. 1993: BR at work: A Computer animation for the 13-14-cis-model of the Photochemical Cycle of Bacteriorhodopsin

91. Transputing ’91, World transputer User Group Conference, Apr. 22–26 (1991), Sun- nyvale, CA, U.S.A.: Parallel Many-Body-Algorithms

92. Alpbach Workshop ‘Protein Structure and Dynamics’, Mar. 12–15 (1990): Applica- tion of Parallel Computing to Molecular Dynamics Simulations for the Photosyn- thetic Reaction Center of Rps. Viridis

Invitations to Colloquia and Seminars

93. Seminar of the Institute of Structural and Molecular Biology, University of Edin- burgh, Prof. Malcolm Walkinshaw, Apr. 17 (2006): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

94. MPIbpc retreat 2006, Uslar, Mar. 3–4 (2006): Force probe molecular dynamics simulations

95. NANOMOT EU meeting, G¨ottingen, Feb. 10/11 (2006): Introduction and Structure of the NANOMOT project

96. Institutskolloquium, Center for Bioinformatics Saar, Univ. des Saarlandes, Dr. B¨ockmann, Feb. 8 (2006): Force probe molecular dynamics of titin activation and bacteriorhodopsin extraction

30 97. Institutskolloquium, Institut fur¨ physikalische Chemie, Univ. Freiburg, Dr. Stein- brecher, Feb. 7 (2006): Ausgekluegelte Poren und komplexe Maschinen: Die Nan- otechnologie der Proteine

98. Institutskolloquium, Biochemische Fakult¨at, Univ. Kassel, Prof. Herberg, Nov. 10 (2005): Ausgekluegelte Poren und komplexe Maschinen: Die Nanotechnologie der Proteine

99. Tag der Physik (Festvortrag, Prof. M. Rief), TU Munc¨ hen, July 1 (2005): Ausgefeilte Poren und komplexe Maschinen: Die Nanotechnologie der Natur

100. Graduiertenkolleg, Fakultät Biologie der Universität Göttingen Prof. Dönecke, Göttingen, June 21 (2005): Molecular dynamics simulations of complex systems

101. Graduiertenkolleg, Fakultät Chemie der Universität Göttingen Prof. Abel, Göttingen, May 18 (2005): Molecular dynamics simulations of complex systems

102. Graduiertenkolleg, Fakultät Chemie der Universität Göttingen Prof. Abel, Göttingen, Dec. 8 (2004): Molecular dynamics simulations of complex systems

103. Physical Chemistry Colloquium, Darmstadt Univ., Prof. Schneider, Oct. 27 (2004): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

104. Lions Club G”ottingen, Dr. Schr”oder, Aug. 24 (2004): Remarks on EU science funding systems

105. Faculty biochemical Colloquium, Leipzig Univ., Prof. Hofmann, June 8 (2004): Elab- orate pores and complex machines: nature’s nanotechnology benchmarks

106. Faculty Colloquium, Marburg Univ., Prof. Klebe, Apr. 27 (2004): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

107. ACTION EU meeting, Copenhagen, Feb. 25/26 (2004): Recent Contributions to Project

108. Meeting of the MPG-CPT-Section, Berlin, Prof. Schl¨ogl, Feb. 20 (2004): Presenta- tion of the Theoretical and Computational Biophysics Department

109. Kuratoriumssitzung am Max-Planck-Institut fur¨ Biophysikalische Chemie G¨ottigen, Prof. Gallwitz, Jan. 23 (2004): Proteins as Nanomachines

110. 39. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 20–25 (2004): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

111. GDCh-Kolloquium Jahr-der-Chemie, Prof. Herges, Kiel, Nov. 20 (2003): Aquapor- ine und ATPasen: Molekulare Maschinen unter der Lupe

112. Maurice-Muller-Symp¨ osium, Basel, Oct. 2–4 (2003): Aquaporines — Complex mov- ing holes

31 113. SFB Colloquium ’Struktur und Funktion membranst”andiger Rezeptoren’, FU Berlin, Berlin, Aug. 27 (2003): Protein Dynamics Simulations: Grasping Molec- ular Nanomachines

114. Physics Colloquium Zurich University, Zurich, June 12 (2003): Protein Dynamics Simulations: Grasping Molecular Nanomachines

115. Workshop of the ’Junge Chemiker Heidelberg’, Heidelberg, May 28 (2003): Protein Dynamics Simulations: Grasping Molecular Nano-Machines

116. Physik-Kolloquium University Beyreut, April 15 (2003): Proteindynamiksimulatio- nen: Molekulare ”Nano-Maschinen” unter der Lupe

117. Graduiertenkolleg, Fakultät Chemie der Universität Göttingen Prof. Abel, Göttingen, Jan. 29 (2003): Molekulardynamische Simulationen von großen biolo- gischen Systemen

118. GDCh-Colloquium, Bielefeld University, Prof. E. Neumann, Dec. 12 (2002): Pro- teindynamiksimulationen: Molekulare ”Nano-Maschinen” unter der Lupe

119. Physics Colloquium, Bremen University, Prof. Richter, Dec. 5 (2002): Proteindy- namiksimulationen: Molekulare ”Nano-Maschinen” unter der Lupe

120. Biophysics Colloquium, Leiden University, Prof. T. Schmidt, Leiden, June 15 (2002): Protein Dynamics Simulations: Grasping Molecular Nano-Machines

121. Kolloquium der Gesellschaft Deutscher Chemiker, Universit¨at Frankfurt, Prof. M. G¨obel, Frankfurt, Feb. 12 (2002): Proteindynamiksimulationen: Molekulare ’Nano- Maschinen’ unter der Lupe

122. Habilitationskolloquium, Universität Göttingen, Prof. Kree (Dekan), Feb. 11 (2002): Der hydrophobe Effekt

123. 37. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 20–25 (2002): Protein Dynamics Simulations: May the Force be with You

124. Seminar of the Chemistry and Biochemistry Department, University of Bern, Prof. Erni, Nov. 19 (2001): Molecular Dynamics Force Probe Simulations: Grasping Molecular Nano-Machines

125. Institute Seminar, Max-Plnack-Institute for Biochemistry, Martinsried, Prof. Baumeister, Nov. 27 (2001): Conformational Dynamics Simulation of Proteins: May the Force be with You

126. Biophysikalisches Kolloquium, University of Dusseldorf,¨ Prof. D. Riesner, Nov. 7 (2001): Proteindynamiksimulationen: Molekulare ’Nano-Maschinen’ unter der Lupe

127. Institute Seminar, Max-Plnack-Institute of Molecular Physiology, Prof. R. Goody, Dortmund, Oct. 15 (2001): Protein Dynamics Simulations: Grasping Molecular Nano-Machines

32 128. Physikalisches Kolloquium, University of Stuttgart, Prof. Trebin, Stuttgart, Oct. 16 (2001): Proteindynamiksimulationen: Molekulare ’Nano-Maschinen’ unter der Lupe

129. Kolloquium fur¨ Bioinformatik, Forschungszentrum Julic¨ h (Germany), Sept. 1 (2001): Proteindynamiksimulationen: Molekulare ’Nano-Maschinen’ unter der Lupe

130. Institute Seminar, Univ. Siegen, Prof. Schwarz, July 16 (2001): Proteindynamik- simulationen: Molekulare ’Nano-Maschinen’ unter der Lupe

131. Institute Seminar, Univ. Wurzburg,¨ Prof. Bayerl, June 14 (2001): Konformationelle Plastizit¨at von Proteinen: Molekulare ’Nano-Maschinen’ unter der Lupe

132. Biophysiktage der Fakultät Physik, Universität Göttingen, Prof. Zippelius, June 13 (2001): Molecular Dynamics Force Probe Simulations and Conformational Motions of Proteins

133. Institute Seminar, EPFL Lausanne, Prof. Margaritondo, May 7 (2001): Molecular Dynamics Force Probe Simulations: Grasping Molecular Nano-Machines

134. Institute Seminar, MPI Dortmund, Prof. Engelhard, March 21 (2001): Molecular Dynamics Force Probe Simulations and Conformational Motions of Proteins

135. 36. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 18–24 (2001) (Chairman)

136. Physics Colloquium, Physics Institute, University of Greifswald, Prof. Th. Klinger, Greifswald, Nov. 9 (2000): Konformationelle Plastizit¨at von Proteinen: Molekulare ’Nano-Maschinen’ unter der Lupe

137. Institute Seminar, Physics Faculty, University of Stuttgart, Prof. J. Wrachtrup, Stuttgart, June 27 (2000): Konformationsdynamik und statistische Mechanik von Proteinen

138. Physics Colloquium, Physics Faculty, Ruhr-Universit¨at Bochum, Prof. Werner Meyer, May 29 (2000): Proteindynamiksimulation: Molekulare Nanomaschinen unter der Lupe

139. Institute Seminar, Institute for Microbiology and Genetics, Universität Göttingen, Prof. Fritz, Göttingen, May 4 (2000): Konformationelle Plastizität von Proteinen und deren Funktion

140. Introductory meeting, Procter&Gamble European Service GmbH, R&D, Dr. Bruno Ehrnsperger, Schwalbach i. Taunus, May 2 (2000): Case study of a molecular dynamics simulation of a polymer in salt solution

141. Institute Seminar, Lehrstuhl fur¨ Theoretische Chemie der Ruhr-Universit¨at Bochum, Prof. Dominik Marx, Apr. 24 (2000): Force Response Simulations: Grasp- ing Molecular Nano-Machines

142. Institute Seminar, MPI for biophysical Chemistry, Dr. Nothdurft, Apr. 7 (2000): Proteine: Maschinen zum Leben

33 143. Institute Seminar, Joint Research Center for Atom Technology, Tsukuba (Japan), Prof. Kiyoyuki Terakura, Mar. 16 (2000): Statistical Mechanics of Structural Tran- sitions in Complex Systems 144. Graduiertenkolleg, Fachbereich Physik der Universität des Saarlandes, Prof. Jurgen¨ Huttermann,¨ Homburg, Feb. 3 (2000): Proteindynamiksimulation: Molekulare Nanomaschinen unter der Lupe 145. 35. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 19–26 (2000): Protein Dynamics Simulations: Grasping Molec- ular Nano-Machines 146. Sonderkolloquium des Fachbereichs Physik der Gerhard-Mercator-Universität Duis- burg, Prof. Dietrich Wolf, Duisburg, Jan. 17 (2000): Proteine: Maschinen zum Leben’ 147. SFB-Seminar of the Lehrstuhl fur¨ Physik Weihenstephan, Technical University of Munich, Prof. Joseph Friedrich, Weihenstephan, Nov. 29 (1999): Protein Dynamics Simulations: Diffusion in Configurational Space 148. Biophysik-Seminar des John von Neumann-Instituts, Forschungszentrum Julic¨ h, Prof. H. Rollnik, Julic¨ h, Germany, Oct. 12 (1999): Conformational Plasticity and Protein Function 149. Biophysical Colloquium of the Faculty of Applied Physics, University of Mu- nich, Prof. Hermann Gaub, Munich, July 30 (1999): ’Force Landscapes’ for Lig- and/Receptor Unbinding — Computation and Reconstruction from Single Molecule Dynamics Force Spectroscopy 150. EMBO Course ’Biophysical and Mathematical Approaches to Cell Biology’, EMBL Heidelberg, July 4–17 (1999): Molecular Dynamics Simulations 151. Tagung des Graduiertenkollegs ‘Dynamik und Evolution zellulärer und makro- molekularer Prozesse’, Prof. G. Damaschun, Hiddensee bei Rugen,¨ Mar. 16–20 (1999): Untersuchung der konformativen Beweglichkeit von Prionen mittels ’conformational flooding’ 152. Göttinger Physikalisches Kolloquium, Universität Göttingen, Prof. G.C. Hegerfeldt, Göttingen, Feb. 8 (1999): Wie funktionieren Proteine? — Nanomaschinen unter der Lupe 153. Group seminar of the Berendsen Group, University of Groningen, Jan. 22 (1999): Predicting Antibody/antigen binding forces and conformational motions in proteins 154. 6. Colloquium of the DFG-Schwerpunkt ‘Neue mikroskopische Techniken fur¨ Biolo- gie und Medizin’, Wildbad-Kreut, Nov. 16–19 (1998): Structural Heterogeneity of Antibody/Antigene Unbinding Pathways 155. SFB-Kolloquium der Universität Freiburg, Biophysikalisches Institut, Prof. Fritz Siebert, Freiburg, Nov. 11 (1998): Unbinding of an Antibody-Hapten Complex Stud- ied by Molecular Dynamics Atomic Force Microscopy Simulations

34 156. DPG-Kurs Physikschulen fur¨ Lehrer 1998 ’Biophysik — Riechen, H¨oren, Sehen, Prof. Peter Fromherz, Bad Honnef, Aug. 17–21 (1998): Proteine: Struktur, Dy- namik, Funktion

157. Theoretisch physikalisches Seminar des Instituts fur¨ theoretische Physik, Prof. Annette Zippelius, G¨ottingen, June 16 (1998): Vorhersage von Ligand-Rezeptor- Bindungskr¨aften und Konformationsbewegungen in Proteinen

158. Biophysics Seminar, University of North Carolina at Chapel Hill, Prof. Jan Hermans, Chapel Hill, U.S.A., Mar. 24 (1998): Computing rupture forces and conformational transitions

159. Computational structural biology seminar at the North Carolina Supercomputing Center, Dr. William Youngblood, Mar. 23 (1998): Fast Molecular Dynamics Methods

160. Kolloquium der Fakult¨at fur¨ Biowissenschaften, Prof. H.-J. Hofmann, Leipzig, Nov. 11 (1997): Molekulardynamiksimulationen von Biomolekulen:¨ Methode — Anwen- dung — Perspektiven

161. Institutskolloquium des Max-Planck-Instituts fur¨ Biophysikalische Chemie, Prof. P. Gruss, G¨ottingen, Sept. 1 (1997): Molekulardynamiksimulationen von Biomolekulen:¨ Methode — Anwendung — Perspektiven

162. Institute Seminar, Department Biochemistry and Biophysics of the Goeteborg Uni- versity, Sweden, Prof. J. Rydstroem, Aug. 28 (1997): Molecular Dynamics Simula- tions of Single Molecule Rupture Experiments

163. Institute Seminar, Chemistry Department of the Swiss Federal Institute of Technol- ogy Zurich (Switzerland), Prof. W. van Gunsteren, Aug. 14 (1997): Predicting Slow Conformational Motions of Proteins: Conformational Flooding

164. Institute Seminar, Institute for Molecular Biology and Biophysics of the Swiss Fed- eral Institute of Technology Zurich (Switzerland), Prof. K. Wuthric¨ h, Sep. 12 (1997): Conformational Flexibility of Prion Protein Fragment 121–231

165. Institute Seminar, Institute for Molecular Biology and Biophysics of the Swiss Fed- eral Institute of Technology Zurich (Switzerland), Prof. R. Glockshuber and Prof. K. Wuthric¨ h, Mar. 7 (1997): Prediction of slow conformational transitions in proteins

166. Regio Seminar, Biozentrum of the University of Basel (Switzerland), Prof. Andreas Engel, Dec. 17 (1996): Protein Dynamics Simulations: Predicting Binding Forces and Conformational Transitions

167. Physics Colloquium, Physics Department, University of Ulm, Prof. Uli Nienhaus, Nov. 11 (1996): Proteindynamiksimulationen zur Vorhersage von Bindungskr¨aften und Konformations¨anderungen in Proteinen

168. Edgar-Lusc¨ her Seminar ‘Biologische Physik’, StD. R. Fichtner, Akademie Dillingen, Oct. 23 (1996): Molekulardynamik-Simulationen molekularbiologischer Systeme

35 169. Bioinformatics Seminar, Genzentrum der Universität Munc¨ hen, Prof. B. Steipe, July 19 (1996): Berechnung von Ligand-Rezeptor-Bindungskräften und Konforma- tionsänderungen in Proteinen

170. Physics Colloquium, Faculty of Physics, University of Linz, Prof. Schindler, Linz (Austria), June 27 (1996): Berechnung von Ligand-Rezeptor-Bindungskr¨aften und Konformations¨anderungen in Proteinen

171. Institute seminar, Institute for Physical Chemistry, Univ. Wurzburg,¨ Prof. Schnei- der, Wurzburg,¨ May 7 (1996): MD-Simulationen: Vorhersage von Ligand-Rezeptor- Bindungskr¨aften und Konformations¨anderungen in Proteinen

172. Informal meeting, Max-Planck-Institut fur¨ Festk¨orperforschung, Stuttgart, Prof. Michele Parrinello, Apr. 16, 1996: Overview on current projects

173. Biophysics Seminar, Cornell University, Ithaca, U.S.A, Prof. David Shalloway, Mar. 6 (1996): Protein Dynamics Simulations: Toward Experimentally Verifyable Pre- dictions

174. Theoretical Biophysics Seminar, Beckman Institute, University of Illinois at Ur- bana/Champaign, U.S.A., Prof. Klaus Schulten, Mar. 4 (1996): Protein Dynamics Simulations: Toward Experimentally Verifyable Predictions

175. Institute seminar, Physik-Department of the Technische Universität Munc¨ hen, Prof. Götze, Munc¨ hen, Feb. 2 (1996): Statistische Mechanik und Strukturvorhersage langsamer Konformationsub¨ ergänge in Proteinen

176. Institute seminar, Physikalisch-Chemisches Institut der Universit¨at Zuric¨ h, Prof. Marco Nonella, Jan. 25 (1996): Predicting Slow Structural Transitions in Macro- molecular Systems: Conformational Flooding

177. 31. Winter Seminar on Molecular Biology and Biophysical Chemistry of the Cell, Klosters, Jan. 13–27 (1996): Theory of Protein Dynamics: Towards Experimentally Verifyable Predictions

178. Institute seminar, Laboratoire de Biophysique Moleculaire et Cellulaire, CENG (Grenoble), Yves Chapron, Nov. 13 (1995): Ligand–Receptor Binding: Molecular Mechanics Calculation of the Streptavidin–Biotin Rupture Force

179. Institute seminar Arbeitsgruppe fur¨ strukturelle Molekularbiologie, Dr. Hans Bar- tunik, DESY, Hamburg, July 24 (1995): Predicting conformational transitions in proteins: Conformational ﬂooding

180. Institute seminar at the Mathematisches Institut der Universit¨at Tubingen,¨ Prof. Lubich, Tubingen,¨ June 1 (1995): Molecular dynamics simulation of proteins: A long way to go

181. Institute seminar at the MPI fur¨ Biologie, Prof. J¨ahnig, Tubingen,¨ June 1 (1995): Predicting slow conformational changes in proteins

36 182. Institute seminar at the Institut fur¨ Medizinische Optik der Universit¨at Munc¨ hen, Prof. Zinth, Munc¨ hen, May 18 (1995): Predicting slow conformational transitions in proteins with conformational ﬂooding

183. Institute seminar at the Institut fur¨ Medizinische Physik und Biophysik, Humboldt- Universit¨at Berlin, Prof. P. Hofmann, Mar. 15 (1995): Predicting slow conformational transitions in proteins

184. Institute seminar, Max-Delbruc¨ k-Centrum fur¨ molekulare Medizin, Berlin-Buch, Dr. Heinz Sklenar, Mar. 13 (1995): Conformational dynamics of a simpliﬁed protein model

185. Weekly seminar of the Chaos Association Munc¨ hen eV, Feb. 20 (1995) Proteins: molecular machines at the interface between order and chaos

186. Graduiertenkolleg, Institut fur¨ Biophysikalische Chemie, Biozentrum der Universit¨at Frankfurt, Prof. Ruterjans,¨ Feb. 16 (1995): Together it’s easier: Molecular dynamics and statistical mechanics of proteins

187. Institute seminar Konrad-Zuse-Zentrum Berlin, Prof. Deufelhard, Feb. 14 (1995): Conformational Dynamics of a Simpliﬁed Protein Model

188. Institute seminar, Max-Planck-Institut fur¨ Biochemie, Prof. P. Fromherz, Martin- sried, Jan. 25 (1995): Conformational dynamics of proteins at long time scales

189. Institute seminar, Laboratoire de Biophysique Moleculaire et Cellulaire, CENG (Grenoble), Yves Chapron, Oct. 14 (1994): Conformational Dynamics of Proteins: Beyond the Nanosecond Time Scale

190. Seminar ‘Proteindynamik’ of the Faculty of Physics, Technical University of Munich, July 1994: Conformational Dynamics of Proteins

191. Institute Seminar of the Sektion Physik, University of Munich, Feb. 8 (1994): Dy- namics simulation of proteins at long time scales

192. 29. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 16–28 (1994): BR at work: A Computer animation for the 13-14-cis-model of the Photochemical Cycle of Bacteriorhodopsin

193. Institute Seminar, Max-Planck-Institut fur¨ Biochemie, Prof. Oesterhelt, Martin- sried, Feb. 11 (1993): Molecular dynamics and visualization of the 13,14-dicis-model in the photo cycle of bacteriorhodopsin

194. Youngster-Meeting of the SFB 143, Munich, May 27 (1992): Computer simulation of biological macromolecules: Methods and limits

195. Beckman Institute Seminar, University of Illinois at Urbana/Champaign, Urbana, IL, U.S.A, 1990: Generalized Verlet-Algorithm for Eﬃcient MD-Simulations with Long-Range-Interactions

37 Other Participations at Conferences and Workshops

196. EICOS, Seminar for Journalists, G¨ottingen, May 30 (2005): Elaborate pores and complex machines: nature’s nanotechnology benchmarks

197. Intersektionelles Sektionssymposium der MPG Berlin, Nov. 25–26 (2004)

198. Annual Biophysics Society Meeting, Baltimore, USA, Feb. 14–19 (2004) (poster contribution)

199. ACTION EU meeting, Aarhus, Nov. 29–30 (2002): Protein structure determination: X-ray vs. electron microscopy

200. ACTION start up EU meeting, Copenhagen, Nov. 16 (2001): Introduction, research goals, research plan

201. Meeting of the VW-Foundation, Physics, Chemistry and Biology with Single Molecules, Staﬀelstein, Germany, March 5–7 (2001): 4 Poster Contributions

202. Aquaplugs start up EU meeting, Amsterdam, Nov. 3–4 (2000): Progress report on structural analysis of aquaporins

203. 3rd International Conference on Molecular Biology and Physiology of Water and Solute Transport, G¨oteborg (Sweden), July 1–5 (2000): The Fold of Aquaporin 1 (poster)

204. Reihe ’Arbeitsgruppen stellen sich vor’ des Max-Planck-Instituts fur¨ Biophysikalis- che Chemie, G¨ottingen, Apr. 7 (2000): Proteine: Maschinen zum Leben

205. EU-Workshop ‘MIP-Family of Channel Proteins’, Biocenter of the University of Basel, Nendaz, Switzerland, Mar. 19–23 (2000): Simulation of Conformational Transitions in Proteins

206. BIOTECH Meeting, CNRS, Gif-sur-Yvette, France, Mar. 12–13 (1999): Progress report on structural analysis of aquaporins

207. Site visit des Wissenschaftlichen Fachbeirats for the MPIbpc, G¨ottingen, Feb. 1 (1999): Protein Function Mechanisms Studied by Molecular Dynamics Simulations

208. Annual Conference of the Deutsche Gesellschaft fur¨ Biophysik, Frankfurt, Sept. 21– 23 (1998): Molecular Dynamics AFM Simulations of an Antibody-Hapten Complex (poster)

209. EU-Workshop ‘MIP-Family of Channel Proteins’, Institute of Anatomy, University of Aarhus, Denmark, Sept. 11–13 (1998): Towards the Structure of AQP 1: Status Report

38 210. EU-Workshop ‘MIP-Family of Channel Proteins’, Lundberg Laboratory, Goeteborg University, Sweden, Aug. 29 (1997): Simulation of Conformational Dynamics of Proteins

211. Spring meeting of the Deutsche Physikalische Gesellschaft (Chemische Physik), Munster,¨ Mar. 17–21 (1997): Predicting slow conformational transitions in proteins

212. Annual Conference of the Deutsche Gesellschaft fur¨ Biophysik, Leipzig, Sept. 18–21 (1996): FAMUSAMM: A new algorithm for eﬃcient computation of electrostatic interactions in molecular dynamics simulations (poster)

213. Spring meeting of the Deutsche Physikalische Gesellschaft (Chemische Physik), Re- gensburg, Mar. 25–29 (1996): Predicting slow structural transitions in disordered macromolecular systems: Conformational Flooding (poster)

214. Spring meeting of the Deutsche Physikalische Gesellschaft (Chemische Physik), Re- gensburg, Mar. 25–29 (1996): Ligand–Rezeptor–Bindung: Molekulardynamiksimu- lationen zur Berechnung der Streptavidin–Biotin–Abreißkraft

215. 2nd International Symposium in Biological Physics, Technical University of Munich, Munich, July 30–Aug. 1 (1995): Prediction of non-local structural transitions in proteins by conformational ﬂooding (talk + poster)

216. 9. Meeting of the Sektion Molekularbiophysik in der Deutschen Gesellschaft fur¨ Biophysik: ‘Polymorphism and Conformational Flexibility of Biological Macro- molecules’, Hunfeld,¨ May 11–14 (1995): Prediction of Slow Conformational Transi- tions in Proteins with Conformational Flooding

217. International Workshop Feldaﬁng III, ’Reaction Centers of Photosynthetic Bacteria: Structure and Dynamics’, Mar 2–4 (1995) (no contribution)

218. 59. Annual Meeting of the Deutsche Physikalische Gesellschaft, Berlin, Mar. 20–24 (1995): Conformational Dynamics of Proteins: A model study (poster)

219. 30. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 14–21 (1995) (no contribution)

220. Annual Meeting of the Deutsche Gesellschaft fur¨ Biophysik, Humboldt-University, Berlin, Sept. 19–21 (1994): Conformational Dynamics of Proteins: A model study (poster)

221. Workshop ‘Nonlinear Excitations in Biomolecules’, Centre de Physique des Houches, France, May 30–June 4, 1994: BR at work: A Computer animation for the 13-14- cis-model of the Photochemical Cycle of Bacteriorhodopsin

222. Workshop ‘Nonlinear Excitations in Biomolecules’, Centre de Physique des Houches, France, May 30–June 4 (1994): Conformational Dynamics of Proteins: Beyond the Nanosecond Time Scale

223. HPCN Europe, Munich, Apr. 18–20 (1994) (no contribution)

39 224. NATO-Workshop ‘Computational Approaches in Supramolecular Chemistry’, Stras- bourg, France, Sept. 1–5 (1993): How Good are Eﬃcient Algorithms for Extended Molecular Dynamics Simulations? (poster)

225. dto.: BR at work: A Computer animation for the 13-14-cis-model of the Photo- chemical Cycle of Bacteriorhodopsin

226. Fortwihr Symposium 1993 ‘Scientiﬁc High Performance Computing’, BMW- Forschungszentrum, Munich, June 17/18 (1993) (no contribution)

227. 12th Annual Conference of the Molecular Graphics Society, ‘Molecular Graphics and the Design of Bioactive Compounds’, Interlaken, June 7–11 (1993): BR at work: A Computer animation for the 13-14-cis-model of the Photochemical Cycle of Bacteriorhodopsin

228. International Conference Molecular Biophysics, Joint Meeting of the Swedish and German Biophysics Societies, Hunfeld,¨ May 13–15 (1993): Eﬃcient Many-Body Algorithms for Molecular Dynamics Simulations of Large Biological Macromolecules (poster)

229. dto.: BR at work: A Computer animation for the 13-14-cis-model of the Photo- chemical Cycle of Bacteriorhodopsin

230. SFB 143-Meeting, Munich, Apr. 1993: Status report of project C1

231. 8. Workshop ‘Biowissenschaften und Information: Computereinsatz in den Biowis- senschaften’, Schloß Birlingshoven, Bonn, Feb. 17 (1993) (no contribution)

232. Bioinformatik Bonn (BIB’93), Feb. 15/16 (1993) (no contribution)

233. 28. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 17–29 (1993) (no contribution)

234. Second Workshop on Parallel Numerical Analysis, University of Edinburgh, GB, June 25–26 (1992): On the Suitability of Eﬃcient Many-Body Algorithms for Molec- ular Dynamics Simulations of Biological Macromolecules

235. 27. Winter Seminar on Molecular Biology and Biophysical Chemistry of Cell Func- tions, Klosters, Jan. 11–25 (1992) (no contribution)

236. 5. Workshop ‘Spectroscopy of Photoreceptors’, Schloß Ringberg, Tegernsee, Oct. 6–10 (1991) (no contribution)

237. Spring Meeting of the Deutsche Physikalische Gesellschaft, Freiburg, Mar. 11–15 (1991): Generalized Verlet Algorithm for Eﬃcient Molecular Dynamics Simulations with Long-Range Interactions

238. International Workshop Feldaﬁng II, ’Structure and Function of Bacterial Reaction Centers’, Mar. 24–26 (1990) (no contribution)

40 Theoretical Molecular Biophysics: Sketch of Research Perspectives

My research is driven by the wish to understand and predict biomolecular processes from first principles, i.e., from the basic laws of physics. Contrary to primarily data-base- driven or purely empirical models, this simulation approach provides causal pictures, and, typically, a much deeper understanding. For biomolecular processes, molecular dynamics type simulations (force field or denisti functional based) are currently — and likely in the near future — the only way to reach this goal. Currently, my focus is on protein dynamics and function. With the picture of a ‘molecular nano-machine’ in mind, we can thus probe and learn how the ‘gears and wheels’ of such machines interact to achieve their function. The rapidly increasing number of avail- able structures opens a wide range of possible studies. Examples are water permeation through aquaporins, mechanical energy transduction in ATP synthase, conformational flexibility of membrane fusion proteins, molecular motor proteins, and enforced dissociation of ligand/receptor complexes like antibodies. At the interface between theoretical physics, structural biology, bioinformatics, and molecular biochemistry, currently two lines of questions characterize my field of interest: (1) How does a given protein work? What is the mechanism of these biochemical ‘nanomachines’? (2) What structural and dynamical properties are common to proteins? What are suitable theoretical, statistical, and computational concepts for the proper description of these highly organized, but irregular pieces of condensed matter? The broader basis offered by a department offers the possibility to widen the scope. One line of new future research is the simulation of supramolecular complexes like DNA/RNA/protein complexes, larger protein complexes, and their interaction with — and influence on — lipid membranes. A particular challenge would be, e.g., to study primary synthesis steps within the ribosome, which likely will become tractable soon, or parts of the spliceosome. Closely related is the long-term challenge to improve the computation of protein/protein or DNA/RNA/protein interactions (as opposed to the heuristical docking methods in bioinformatics), thereby providing essential input for the study of genetic regulation or metabolic networks. A second focus will be the study of chemical reactions in biomolecules, particularly enzymatic catalysis and charge transfer reactions. These cannot be described by the con- ventional force field based molecular dynamics techniques. Recently, density functional and Car-Parrinello techniques have matured sufficiently to describe those regions of an en- zyme quantum-mechanically, where the chemical reactions of interest take place, whereas the remainder of the protein is described classically. Such hybrid approach trades off the complexity and the size of a protein and the effort of a quantum-mechanical description. Thirdly, and following-up the recently improved hierarchical classification of proteins structures, we will likely be soon in the position to systematically scan and classify the conformational dynamics of larger numbers of protein structures, thus enhancing our general understanding of the statistical mechanics of conformational motions, which are the elementary steps of protein function. It is my hope that such studies will not only answer questions that pertain to specific proteins, but in the long run will also help to extend the hierarchy of methods to describe and compute biomolecular dynamics and function towards the mesoscopic scale. A further example for future research is structure determination. Traditionally, molec-

41 ular dynamics simulations are widely used as a tool to search for those structures which best match NMR or x-ray data. We and others have recently shown that extended un- constrained simulations can also be used for structure validation especially in cases where relatively low resolution is achieved, such as in cryo electron microscopy. As this technique is particularly strong for the structure determination of membrane proteins, we would like to engage more deeply in their refinement. From the methodological point of view, understanding biomolecular function requires work in classical mechanics, electrostatics, statistical mechanics, quantum mechanics, bioinformatics, and computer science. Up to now there is no unifying ‘protein theory’; rather, there is a patch-work of methods and concepts describing different facets of these complex systems, which are continuously improved and refined. Accordingly, success depends on the ability improve, to apply, to combine, and to implement a large number of such ‘patches’. To sharpen and to test these tools, close contact to as many experimental data as possible is essential. Thus, an important line of research is the simulation — and stimulation — of atomic force microscopy, optical tweezers, or single molecule (FRET) spectroscopy experiments. Typically, such simulations provide a microscopic interpretation of the mea- sured data that could not be obtained by the experiment alone. Nearly all of my projects involve close collaborations with experimental groups, much to the benefit of the projects. Today, essentially all current molecular dynamics studies face the sampling problem — i.e., that the simulation time scale is too short — as a critical and, quite often, limiting factor. In 1975, typical simulation time scales were a few picoseconds; today, the world record is a microsecond, and tens to hundreds of nanoseconds will be routine soon. Yet, to make contact to microseconds or even milliseconds biomolecular processes, a number of tricks and assumptions are still necessary to bridge this time scale gap. With the expected future increase in computer power and known structures, and with further advances in the theory of essential degrees of freedom, however, a considerable fraction of biomolecular processes will become accessible to molecular dynamics simulations within the next years. But the slower accessible time scales get, the smaller are the energy gradients that drive these processes, and the higher accuracy is required for the force fields used in the simulations. The need for more accurate force fields will, therefore, likely replace the sampling problem as the main simulation bottleneck. Work on the improvement of force fields will therefore also be mandatory. Given the unique combination of experimental approaches and possible collaborations at the Max Planck Institute for Biophysical Chemistry and the other Göttingen Insti- tutes, and equipped with competitive high performance parallel computer hardware as well as with the infrastructure and continuity to develop new methods, software, and force fields, a Theoretical Molecular Biophysics Department would join forces to study an increasing number of biomolecular processes, to provide first principles interpretations of experiments, to advance structure refinement and prediction methods, and to improve the theoretical concepts for biomolecular dynamics. After the explosive growth of known sequences and known biomolecular structures, and with the rapid improvement of single molecule techniques, the challenge is now to similarly expand our knowledge on biomolecular dynamics and function at the atomic level. See also http://www.mpibpc.mpg.de/abteilungen/070.