Curriculum Vitae Anna Jagielska, Ph.D.

Curriculum Vitae

Anna Jagielska, Ph.D.

Address

Correspondence 4160 Cedar Knoll Drive Tucker, GA 30084 (770) 934-4793

Work Department of Biological and Agricultural Engineering University of Georgia 195 Riverbend Research South 220 Riverbend Road Athens, GA 30602 (770) 630-8891 Tel. (706) 542-8806 Fax [email protected] http://www.uga.edu/xulab/index.htm

Education

Ph.D., Chemistry, Warsaw University, Warsaw, Poland, 2001 Advisor: Prof. Lucjan Piela Thesis: "Theoretical investigation of linear donor-acceptor systems – toward building a molecular memory".

M. Sc., Chemistry, Warsaw University, Warsaw, Poland, 1995 Advisor: Prof. Marek Trojanowicz Thesis: “Amperometric biosensor for detection of phenols”.

Research Interests Nano-Bioengineering, Single-Molecule Studies of Biological Systems using Atomic Force Microscopy, applications for research. Development of accurate Force Fields for Molecular Simulations using global optimization and quantum mechanical calculations. structure refinement, protein-protein, protein-ligand interactions. Development of computational Methods to Simulate a Cell or cell compartments using muti-scale modeling. Targeted Drug Delivery using Synthetic Biology. Development of computational methods for rational design of components (parts) for synthetic biology (e.g. enzymes), having improved or novel activities, with a goal to use the designed parts to engineer cells for therapeutic tasks, such as targeted drug delivery to a tumor.

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Design, computational modeling and synthesis of Multi-task Therapeutic Macromolecules, for delivering a drug specifically to the disease site and inducing an immunological response at the disease site. Rational . Identifying potential drug targets using biological pathways (including information about differences in levels of , mRNAs, and metabolites between healthy and diseased cells). Computational design of drug molecules that will enable controlled regulation of pathways that are critical for a disease. Design and building of Artificial Biological Networks based on synthetic biology that could simulate behavior of human biological networks for testing the newly designed drugs. Computational design of Highly Specific Molecular Sensors to track levels of biomolecules in living cells. One of the goals would be to build a chip with nano- needles carrying the sensors and to monitor concentration of molecules in different compartments of a living cell in real time (e.g., to analyze changes in levels of proteins after applying a drug). Computational design and synthesis of Molecular Memory for electronics based on bi-stability of electronic states of a molecule.

Professional Experience 2008-present Postdoctoral Associate at Dr. Bingqian Xu group, Nano- Bioengineering Lab, Department of Biological and Agricultural Engineering, University of Georgia, Athens, GA. Research in the field of nano-bioengineering and single-molecule study of biological systems using Atomic Force Microscopy, application to development of cancer therapies.

2006-2008 Postdoctoral Associate at Dr. Jeffrey Skolnick group, Center for the Study of , Georgia Institute of Technology, Atlanta, GA. Research in the field of prediction, development of force fields for proteins, and cancer targeting with peptide mimetics.

2005–2006 Postdoctoral Associate at Dr. Jeffrey Skolnick group, Center of Excellence in , University at Buffalo, Buffalo, NY. Research in the field of protein structure prediction and development of force fields.

2004–2005 Research Associate at Dr. Harold A. Scheraga group, Baker Laboratory, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY. Research in the field of protein folding and protein structure prediction, and development of force fields.

2001–2004 Postdoctoral Associate at Dr Harold A. Scheraga group, Baker Laboratory, Chemistry and Chemical Biology Department, Cornell University, Ithaca, NY. Research in the field of protein folding and protein structure prediction, and development of force fields.

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1995–2001 Graduate Student/Teaching Assistant at Prof. Lucjan Piela group, Quantum Chemistry Laboratory, Department of Chemistry, Warsaw University, Warsaw, Poland. Research in the field of applied quantum chemistry, design of molecular memory based on bi-stable quantum systems.

Collaborated with both theoretical and experimental research groups.

Teaching Experience 1995-1998 Teaching Assistant, Quantum Chemistry Laboratory, Department of Chemistry, Warsaw University, Warsaw, Poland. Classes and supplemental lectures in Quantum Chemistry (six semesters), supervising undergraduate students. 1999-2000 Teaching the preparation courses for SAT – Chemistry; high success rate. 1999-2000 Tutoring high school students at youth camps for scientifically talented children.

Grant Writing Experience

"Theoretical investigations of linear donor-acceptor systems”, submitted to Polish Scientific Committee, 1998-1999 – funded (wrote the grant, in collaboration with Prof. L. Piela, Warsaw University) “Peptide-Targeted Inhibition of the EphA2 Receptor Tyrosine Kinase in Epithelial Ovarian Cancer”, to be submitted to Department of Defense, 2008, (participated in writing, in collaboration with Dr. E. B. Dickerson, ) Computational units grants “Design and parameterization of a force field and global optimization procedure for ab-initio protein structure prediction based on a hierarchical structure of the energy landscape”, submitted to Pittsburgh Supercomputer Center, 2002-2005, granted for three consecutive years (participated in writing, in collaboration with Dr. H. A. Scheraga, Cornell University) “Refinement of predicted low-resolution protein models to high-resolution all-atom structures”, submitted to Pittsburgh Supercomputer Center, 2005-2007 – granted for two consecutive years (wrote the grant, in collaboration with Dr. J. Skolnick, Georgia Tech)

Honors and Awards

1999 Erasmus Scholarship at Prof. Jean-Marie Andre group, Facultes Universitaires Notre-Dame de la Paix, Namur, Belgium (Research field: Quantum Chemistry). 1998-1999 Grant of the Polish Scientific Committee (KBN) for Outstanding Graduate Research (Research field: Quantum Chemistry). 1995 Undergraduate student fellowship, Umeå University, Umeå, Sweden (Research field: Analytical Chemistry).

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1994 Undergraduate student fellowship, Technical University of Berlin, Berlin, Germany (Research field: Analytical Chemistry)

Expertise and Technical Skills

Theoretical expertise Protein structure and protein folding prediction, refinement of protein models using physics-based potentials Molecular modeling techniques including Molecular Dynamics, Langevin Dynamics, Monte Carlo, Replica Exchange simulations Development of physics and knowledge-based force fields for molecular simulations and protein structure refinement Development of efficient sampling methods for protein structure prediction Design of molecular memory based on bi-stability of electronic states Quantum chemistry and theory of molecular interactions, quantum chemical calculations for molecules Passive knowledge in using of biological pathways to determine potential drug targets in therapies. Experimental expertise Design and construction of biosensors using enzymes and flow injection amperometric analysis. Atomic Force Microscopy measurements of biological systems, including protein- ligand interactions immobilized on substrate, and in living cells. Technical skills and coursework Fortran programming, Awk, Unix, Linux, Windows Extensive familiarity with Gaussian, Gamess, Amber, UNRES, ECEPP, and TASSER programs Large-scale calculations using large computer clusters (used: 4000-processor IBM cluster at Georgia Tech, Pittsburgh Supercomputer Center and Teragrid computers) Coursework includes: General Chemistry, Organic Chemistry, Physical Chemistry, Statistical Mechanics, Quantum Chemistry, Analytical Chemistry, Biochemistry, Electrochemistry, Spectroscopy, Chemical Technology, Radiology, Physics, Crystallography, Algebra, Calculus, Immunology

Research Accomplishments

Derived a new force field for ab-initio crystal structure prediction of organic molecules and protein structure prediction (ECEPP-5) using the global optimization method. The force field correctly predicted the experimental crystal structure for 80% of tested molecules and outperformed other existing force fields for crystal structure prediction (collaboration with Dr. Harold A. Scheraga group, Cornell University) (7, 13, 14) Helped, using molecular calculations and modeling, to resolve a pattern of disulfide bonds and determine the NMR structure of the somatomedin B domain of human vitronectin (PDBid: 1ssu). Vitronectin is a glycoprotein participating in multiple cellular signaling processes including cancer growth and metastasis. (collaboration

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with Dr. Jane Dyson, Scripps Institute, and Dr. Harold A. Scheraga, Cornell University) (12) Demonstrated that the observed folding pathways of protein A may depend on temperature used in experiment or simulations, which could explain the discrepancies between reported results for folding of protein A. (collaboration with Dr. Harold A. Scheraga, Cornell University) (4) Demonstrated that current popular all-atom physics-based force fields, such as Amber or Charmm give inaccurate values of relative energies of helices versus strands in proteins (the basic elements of protein structure), which is one of the reasons for a frequent failure of these potentials in protein structure predictions. Showed, that these potentials are, however, mathematically capable of correct description of the relative stability of the helices and strands. Therefore, inaccuracies of these potentials can be fixed by their reoptimization. (collaboration with Dr. Jeffrey Skolnick, Georgia Tech) (5) Demonstrated, using quantum mechanical calculations, that the relative stability of a helix versus extended structure in proteins is only weakly dependent on amino acid identity. Therefore, observed preferences of some amino acids to adopt either helical or extended conformation in protein structures must depend of non-local interactions in proteins or interactions with solvent. (5) Achieved a great improvement in scoring and refining of protein decoy structures, by using global optimization method of the commonly used Amber ff03 force field. The correlation coefficient between energy and native similarity of protein decoys improved from 0.25 to 0.65 on average, and scoring of native structure as the lowest in energy improved from 22 to 90%, on average, for large set of proteins. Demonstrated importance of accurate hydrogen bond potential in recognizing the native structure as the lowest energy one and improving the correlation of energy with native similarity. (2) Demonstrated for the first time systematic and significant refinement of all-atom protein structures for large set of proteins and their decoys. Developed efficient conformational sampling method and applied the globally optimized physics-based force field to refine protein models. This is the first achievement of systematic refinement of protein structures for significant number of proteins using physics- based potential, the task that was untraceable before. (1) Determined the necessary conditions for linear donor-acceptor systems to reveal the bi-stability of electronic states and to be a potential material for molecular memory (collaboration with Prof. Lucjan Piela, Warsaw University, Poland) (16, 17, 21) Proposed the first molecular systems that satisfy the conditions for electronic bi- stability and proved for the first time, using rigorous quantum chemical calculations, existence of electronic bi-stability in real molecules (16, 17) Demonstrated, using quantum mechanical calculations, that the external electric field can modulate the energetic barrier between the two states of molecular memory and could also be used as a switch between the memory states. (Ph.D. Thesis) Showed that sufficient electric field to modulate the energy barrier between the memory states could be introduced by the molecular scaffold holding donors and acceptors (e.g. protein -helix) or by localized charge introduced for instance by a tip of Atomic Force Microscope. (Ph.D. Thesis)

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Publications

1. A. Jagielska, L. Wroblewska, and J. Skolnick, “Refinement of Protein Models using Physics-based All-Atom Force Field”, PNAS, 2008, 105, 8268-8273.

2. A. Jagielska, L. Wroblewska, and J. Skolnick, “Development of Physics-based Force Field for Scoring and Refinement of Protein Models”, Biophys. J., 2008, 94, 3227-3240.

3. E. B. Dickerson, A. Jagielska, M. Akhtar, L. Wroblewska, L. B. Kapa, N. J. Bowen, J. M. McDonald, “Altering signaling pathways of EphA2 by use of a peptide-mimetic”, in preparation.

4. A. Jagielska and H. A. Scheraga, “Influence of temperature, friction, and random forces on folding of the B-domain of Staphylococcal Protein A. All-atom molecular dynamics in implicit solvent”, 2007, J. Comp. Chem. 28, 1068-1082.

5. A. Jagielska and J. Skolnick, “Origin of intrinsic helix versus strand stability in homopolypeptides and its implications for the accuracy of the Amber force field.”, 2007, J. Comp. Chem., 28, 1648–1657.

6. J. Makowska, K. Baginska, M. Makowski, A. Jagielska, A. Liwo, F. Kasprzykowski, L. Chmurzynski, H. A. Scheraga, “Assesment of two theoretical methods to estimate potentiometric-titration curves of peptides: comparison with experiment”, 2006, J. Phys. Chem. B., 110, 4451-4458.

7. Y. Arnautova, A. Jagielska, and H. A. Scheraga, “A New Force Field (ECEPP-05) for Peptides, Proteins, and Organic Molecules”, 2006, J.Phys.Chem. B, 110, 5025-5044.

8. S. Oldziej, C. Czaplewski, A. Liwo, M. Chinchio, M. Nanias, J. A. Vila, M.Khalili, Y. A. Arnautowa, A. Jagielska, M. Makowski, H. D. Schafroth, R. Kazmierkiewicz, D. R. Ripoll, J. Pillardy, J. A. Saunders, Y. K. Kang, K. D. Gibson, and H. A. Scheraga, “Physics-based protein-structure prediction using a hierarchical protocol based on the UNRES force field – test with CASP5 and CASP6 targets”, 2005, Proc. Natl. Acad. Sci. USA, 102, 7547-7552.

9. H. A. Scheraga, A. Liwo, S. Oldziej, C. Czaplewski, J. Pillardy, D. R. Ripoll, J. A. Vila, R. Kazmierkiewicz, J. A. Saunders, Y. A. Arnautova, A. Jagielska, M. Chinchio, M. Nanias, “The protein folding problem: Global optimization of force fields”, 2004, Frontiers in Bioscience, 9: 3296-3323 Suppl. S, SEP 1.

10. J. Makowska, K. Baginska, F. Kasprzykowski, J. A. Vila, A. Jagielska, A. Liwo, L. Chmurzynski, H. A. Scheraga, “Interplay of charge distribution and conformation in peptides: Comparison of theory and experiment”, 2005, Biopolymers, 80, 214-224.

11. M. Khalili, A. Liwo, A. Jagielska, and H. A. Scheraga, “Molecular Dynamics with the united-residue (UNRES) model of polypeptide chains. II Langevin and Berendsen bath dynamics and tests on model -helical systems”, 2005, J. Phys. Chem.B, 109, 13798-13810.

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12. Y. Kamikubo, R. De Guzman, G. Kroon, S. Curriden, J. G. Neels, M. J. Churchill, P. Dawson, S. Oldziej, A. Jagielska, H. A. Scheraga, D. J. Loskutoff, and J. Dyson, “Disulfide Bonding Arrangements in Active Forms of the Somatomedin B Domain of Human Vitronectin”, 2004, Biochemistry, 43, 6519-6534.

13. A. Jagielska, Y. A. Arnautova, H. A. Scheraga, “Derivation of a new force field for crystal- structure prediction using global optimization: nonbonded potential parameters for amines, imidazoles, amides, and carboxylic acids”, 2004, J. Phys. Chem. B, 108, 12181-12196.

14. Y. A. Arnautova, A. Jagielska, J. Pillardy, and H. A. Scheraga, “Derivation of a new force field for crystal-structure prediction using global optimization: nonbonded potential parameters for hydrocarbons and alcohols”, 2003, J. Phys. Chem. B, 107, 7143-7154.

15. T. Kasprzycka–Guttman, E. Megiel, A. Jagielska, L. Wroblewska, “Association of pyridine and its methyl derivatives. A theoretical and experimental study.”, 2001, J. Mol. Struct., 569, 111-119.

16. W. Grochala, A. Jagielska, K. Wozniak, R. Bilewicz, A. Bulinska, B. Korybut- Daszkiewicz, J. Bukowska, L. Piela, "Neutral Ni(II) and Cu(II) Complexes of Tetraazatetraenemacrocycles", 2001, J. Phys. Org. Chem., 14, 63-73.

17. A. Jagielska, L. Piela, "Electrostatically Driven Electronic Molecular Bistability", 2000, J. Chem. Phys., 112, 2579-2585.

18. A. Jagielska, R. Moszynski, L. Piela, "A Large Structural Polarization by Intermolecular

Forces. Ab Initio Theoretical Investigation of the H3N...BH2CN and H3N...B(CN)3 Interactions", 1999, Int. J. Quantum Chem., 75, 177-185.

19. A. Jagielska, R. Moszynski, L. Piela, "Ab Initio Theoretical Study of Interactions in Borazane Molecule", 1999, J. Chem. Phys. 110, 947-954.

20. M. Trojanowicz, A. Jagielska, P. Rotkiewicz, A. Kierzek “Flow-Injection Determination of Phenols with Tyrosinase Amperometric Biosensor and Data Processing by Neural Network”, 1999, Chem. Anal., 44, 865-878.

21. A. Jagielska, L. Piela, L. Z. Stolarczyk, "Mnemon-A Hypothetical Molecule with Bistable Electronic Ground State", Proceeding of the 1st International. Conference on Rough Sets and Current Trends in Computing (RSCTC), Warsaw 1998, 1-3.

Book Chapters

22. H. A. Scheraga, A. Liwo, S. Oldziej, C. Czaplewski, J. Pillardy, J. Lee, D. R. Ripoll, J.A. Vila, R. Kazmierkiewicz, J. A. Saunders, Y. A. Arnautova, K. D. Gibson, A. Jagielska, M. Khalili, Chinchio, M. Nanias, Y. K. Kang, H. Schafroth, A. Ghosh, R. Elber, and M. Makowski, Book chapter in “New Algorithms for Macromolecular Simulations”, 2006, Springer, “The Protein Folding Problem”, p.89-103.

Invited Talks

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„Refinement of protein structures using physics based force fields”, October 2007, Georgia Institute of Technology.

„State of the art in protein structure prediction: refinement of protein models”, March 2008, University of Georgia.

“State of the art in protein structure prediction: refinement of protein models”, April 2008, University of Chicago.

„Combining Atomic Force Microscopy and to develop peptide- based cancer therapy”, November 2008, University of Georgia.

References

Dr. Harold A. Scheraga Baker Laboratory of Chemistry and Chemical Biology Cornell University Ithaca, NY 14853-1301 USA Tel: (607) 255-4034 Fax: (607) 254-4700 E-mail: [email protected]

Dr. Erin Dickerson Georgia Cancer Coalition Distinguished Cancer Scientist IBB/Ovarian Cancer Institute Georgia Institute of Technology 315 Ferst Drive Atlanta, GA 30332 Tel: (404) 385-6628 office, (404) 385-6631 lab E-mail: [email protected]

Dr. Bingqian Xu Faculty of Engineering and NanoSEC Department of Biological and Agricultural Engineering University of Georgia 507 Driftmier Engineering Center/168 Riverbend Research South Athens, GA 30602 Tel: (706) 542-0502 Fax: (706) 542-9476 E-mail: [email protected], Web: http://www.uga.edu/xulab

Dr. Jeffrey Skolnick Center for the Study of Systems Biology, School of Biology Georgia Institute of Technology th 250 14 Street, NW, Room 138 Atlanta, GA 30318

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Tel: (404) 407-8975 Fax: (404) 385-7478 E-mail: [email protected], http://cssb.biology.gatech.edu

Dr. Ying Xu Department of Biochemistry and Molecular Biology A110, Life Science Building 120 Green Street University of Georgia Athens, GA 30602-7229 Phone: 706-542-9779, 706-542-7783 Fax: 706-542-9751/7782 E-mail: [email protected] http://csbl.bmb.uga.edu/~xyn/

Prof. Lucjan Piela Quantum Chemistry Laboratory Chemistry Department Warsaw University Pasteura 1, 02-098 Warsaw, Poland Tel: +48 22 822-0211 ext. 525 Fax: +48 22 822-2309 E-mail: [email protected]

Dr. Jaroslaw Meller Department of Environmental Health University of Cincinnati College of Medicine PO Box 670056 Cincinnati, Ohio 45267-0056 Tel: (513) 558-1958, (513) 636-0270 Fax: (513) 558-4397, (513) 636-2056 E-mail: [email protected]

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