Synthesis and Structural Studies of Cyclic Py-Im Polyamides
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Protein-Ligand Interactions from Molecular Recognition to Drug Design
P ) . .~ " r~- O Protein-Ligand Interactions From Molecular Recognition to Drug Design Edited by H.-J. Bohm and C. Schneider WILEY- VCH WILEY-VCH GmbH & Co. KGaA Contents Preface XI A Personal Foreword XIII List of Contributors XV List of Abbreviations XVII Prologue 1 David Brown 1 Prediction of Non-bonded Interactions in Drug Design 3 H.-J. Bohm 1.1 Introduction 3 1.2 Major Contributions to Protein-Ligand Interactions 4 1.3 Description of Scoring Functions for Receptor-Ligand Interactions 8 1.3.1 Force Field-based Methods 9 1.3.2 Empirical Scoring Functions 9 1.3.3 Knowledge-based Methods 11 1.4 Some Limitations of Current Scoring Functions 12 1.4.1 Influence of the Training Data 12 1.4.2 Molecular Size 13 1.4.3 Water Structure and Protonation State 13 1.5 Application of Scoring Functions in Virtual Screening and De Novo Design 14 1.5.1 Successful Identification of Novel Leads Through Virtual Screening 14 1.5.2 De novo Ligand Design with LUDI 25 1.6 Outlook 16 1.7 Acknowledgments 17 1.8 References 17 VI Contents 2 Introduction to Molecular Recognition Models 21 H.-J. Schneider 2.1 Introduction and Scope 21 2.2 Additivity of Pairwise Interactions - The Chelate Effect 22 2.3 Geometric Fitting: The Hole-size Concept 26 2.4 Di- and Polytopic Interactions: Change of Binding Mechanism with Different Fit 28 2.5 Deviations from the Lock-and-Key Principle 30 2.5.1 Strain in Host-Guest Complexes 30 2.5.2 Solvent Effects 30 2.5.3 Enthalpy/Entropy Variations 31 2.5.4 Loose Fit in Hydrophobically Driven Complex Formation 32 2.6 Conformational Pre-organization: Flexible vs. -
Molecular Recognition and Advances in Antibody Design and Antigenic Peptide Targeting
International Journal of Molecular Sciences Editorial Molecular Recognition and Advances in Antibody Design and Antigenic Peptide Targeting Gunnar Houen and Nicole Trier * Department of Neurology, Rigshospitalet Glostrup, Nordre Ringvej 57, 2600 Glostrup, Denmark; [email protected] * Correspondence: [email protected] Received: 11 February 2020; Accepted: 15 February 2020; Published: 19 February 2020 Molecular recognition, the specific interaction between molecules by a combination of physical forces, has been a subject of scientific investigation for decades. The physical forces involve a combination of dipole-dipole interactions (van der Waals forces), hydrogen bonds and ionic interactions, and it is the optimal spatial combination of these interactions, that defines the specificity, i.e., the strength of the interaction, measured as an affinity constant, defined by the association and dissociation rate constants: Ka = kon/koff [1–3]. Specific interactions in living organisms are numerous, ranging from base pairing in DNA and RNA, protein folding, protein interactions and many more, constituting the basis of life [4–6]. Molecular recognition of foreign substances (self/non-self recognition) is the basis of immune defense against pathogens, spanning from less specific (promiscuous) MHC-peptide interactions to highly specific T cell (antigen) receptor (TCR) recognition of MHC-peptide complexes and from less specific IgM-antigen interactions to highly specific IgG-antigen interactions [7–9]. Through the study of the aforementioned specific interactions, scientists have learned to use natural molecules as reagents and have developed new reagents based on the same principles and physical forces. This issue of IJMS, entitled “Advances in Antibody Design and Antigenic Peptide Targeting” aims to give a status of the current “state-of-the-art” in specific molecular recognition. -
Introduction to the Molecular Recognition and Self-Assembly Special Feature
SPECIAL FEATURE: INTRODUCTORY PERSPECTIVE Introduction to the Molecular Recognition and Self-Assembly Special Feature Julius Rebek, Jr.1 The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037 olecular recognition is a ist. On mixing, these 2 capsules form a and departures for possible future mature branch of chemical hybrid, which is more stable than ei- applications. science, and why shouldn’t ther original capsule. The formation of A switching device is involved in a it be? Decades of studies in the hybrid provides places for guests calyx[6]arene that offers 2 separate Mphysical organic chemistry have defined that could not otherwise be accommo- binding sites in the work of Coquie`re et and evaluated the weak intermolecular dated. As in certain schools of archi- al. (6), ‘‘Multipoint molecular recogni- forces involved when 2 molecules en- tecture, reversible encapsulation is less tion within a calix[6]arene funnel com- counter each other. Every bimolecular about the mechanical boundaries of plex.’’ The conformational mobility of reaction, whether it occurs in the gas the walls than it is about the spaces the system allows 3 imidazole arms to phase, dilute solution, or an enzyme’s they define. chelate zinc ions, while 3 aniline nitro- interior, begins with a recognition event. Encapsulation of multiple groups of gens converge to provide a binding site It is an apt time to explore recognition small molecules is the theme of the arti- for a single proton. The space in the in a larger context, that of multicompo- cle by Yamauchi et al. -
Design of Molecular Mechanics Modeling Techniques for Exploring Molecular Recognition Using Cyclodextrins
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 12-2003 “Design of Molecular Mechanics Modeling Techniques For Exploring Molecular Recognition Using Cyclodextrins. Shannon Bradley Fox University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Chemistry Commons Recommended Citation Fox, Shannon Bradley, "“Design of Molecular Mechanics Modeling Techniques For Exploring Molecular Recognition Using Cyclodextrins.. " PhD diss., University of Tennessee, 2003. https://trace.tennessee.edu/utk_graddiss/2013 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Shannon Bradley Fox entitled "“Design of Molecular Mechanics Modeling Techniques For Exploring Molecular Recognition Using Cyclodextrins.." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Chemistry. M. J. Sepaniak, Major Professor We have read this dissertation and recommend its acceptance: Elizabeth Howell, S. D. Gilman, Z. Xue Accepted -
1993 Human Genome Program Report
Please address queries on this publication to: Human Genome Program U.S. Department of Energy Office of Health and Environmental Research ER-72 GTN Washington, DC 20585 301/903-6488, Fax: 301/903-8521 Internet: [email protected] Human Genome Management Information System Oak Ridge National Laboratory P.O. Box 2008 Oak Ridge, TN 37831-6050 615/576-6669, Fax: 615/574-9888 BITNET: bkq@ornlstc Internet: [email protected] This report has been reproduced directly frorn the best obtainable copy. Available to DOE and DOE contractors from the Office of Scientific and Technical Information; P.O. Box 62; Oak Ridge, TN 37831. Price information: 615/576-8401 . Available to the public from the National Technical Information Service; U.S. Department of Commerce; 5285 Port Royal Road; Springfield, VA 22161. DOE/ER-0611 P uman nome 1993 Program Report Date Published: March 1994 U.S. Department of Energy Office of Energy Research Office of Health and Environmental Research Washington, D.C. 20585 Preface he purpose of this report is to update the Human Genome 1991-92 Program Report T (DOE/ER-0544P, published June 1992) and provide new information on the DOE genome program to researchers, program managers, other government agencies, and the interested public. This FY 1993 supplement includes abstracts of 60 new or renewed projects and listings of 112 continuing and 28 completed projects. These two reports, taken together, present the most complete published view of the DOE Human Genome Program through FY 1993. Research is progressing rapidly toward the 15-year goals of mapping and sequencing the DNA of each of the 24 different human chromosomes. -
Receptor Compaction and Gtpase Movements Drive Cotranslational Protein Translocation
bioRxiv preprint doi: https://doi.org/10.1101/2020.01.07.897827; this version posted January 8, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Receptor compaction and GTPase movements drive cotranslational protein translocation Jae Ho Lee1, SangYoon Chung2, Yu-Hsien Hwang Fu1,a, Ruilin Qian1,b, Xuemeng Sun1,c, Shimon Weiss2,3, Shu-ou Shan1* 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 2Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095 3Department of Physics, Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 52900, Israel aCurrent address: Department of Biochemistry, Stanford University, Stanford, CA, 94305 bCurrent address: Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China cCurrent address: Department of Chemistry, Princeton University, Princeton, NJ, 08544 *corresponding author. Email: [email protected] Keywords: Protein Targeting, Signal Recognition Particle, Single Molecule Spectroscopy, GTPase, Ribosome, Protein Dynamics Short Title: SRP receptor compaction drives protein targeting bioRxiv preprint doi: https://doi.org/10.1101/2020.01.07.897827; this version posted January 8, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Signal recognition particle (SRP) is a universally conserved targeting machine that couples the synthesis of ~30% of the proteome to their proper membrane localization1,2. -
From Genomics to Scientomics: Expanding the Bioinformation Paradigm
Information 2011, 2, 651-671; doi:10.3390/info2040651 OPEN ACCESS information ISSN 2078-2489 www.mdpi.com/journal/information Article From Genomics to Scientomics: Expanding the Bioinformation Paradigm Raquel del Moral, Mónica González, Jorge Navarro and Pedro C. Marijuán * Bioinformation and Systems Biology Group Instituto Aragonés de Ciencias de la Salud (I+CS), 50009 Zaragoza, Spain; E-Mails: [email protected] (R.M.); [email protected] (M.G.); [email protected] (J.N.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: (0034) 976 713 526; Fax: (0034) 976 715 554. Received: 1 September 2011; in revised form: 31 October 2011 / Accepted: 1 November 2011 / Published: 9 November 2011 Abstract: Contemporary biological research (particularly in systems biology and the “omic” disciplines) is factually answering some of the poignant questions associated with the information concept and the limitations of information theory. Here, rather than emphasizing and persisting on a focalized discussion about the i-concept, an ampler conception of “informational entities” will be advocated. The way living cells self-produce, interact with their environment, and collectively organize multi-cell systems becomes a paradigmatic case of what such informational entities consist of. Starting with the fundamentals of molecular recognition, and continuing with the basic cellular processes and subsystems, a new interpretation of the global organization of the living cell must be assayed, so that the equivalents of meaning, value, and intelligence will be approached along an emerging “bioinformational” perspective. Further insights on the informational processes of brains, companies, institutions and human societies at large, and even the sciences themselves, could benefit from—and cross-fertilize with—the advancements derived from the informational approach to living systems. -
Celebrating 40 Years of Rita Allen Foundation Scholars 1 PEOPLE Rita Allen Foundation Scholars: 1976–2016
TABLE OF CONTENTS ORIGINS From the President . 4 Exploration and Discovery: 40 Years of the Rita Allen Foundation Scholars Program . .5 Unexpected Connections: A Conversation with Arnold Levine . .6 SCIENTIFIC ADVISORY COMMITTEE Pioneering Pain Researcher Invests in Next Generation of Scholars: A Conversation with Kathleen Foley (1978) . .10 Douglas Fearon: Attacking Disease with Insights . .12 Jeffrey Macklis (1991): Making and Mending the Brain’s Machinery . .15 Gregory Hannon (2000): Tools for Tough Questions . .18 Joan Steitz, Carl Nathan (1984) and Charles Gilbert (1986) . 21 KEYNOTE SPEAKERS Robert Weinberg (1976): The Genesis of Cancer Genetics . .26 Thomas Jessell (1984): Linking Molecules to Perception and Motion . 29 Titia de Lange (1995): The Complex Puzzle of Chromosome Ends . .32 Andrew Fire (1989): The Resonance of Gene Silencing . 35 Yigong Shi (1999): Illuminating the Cell’s Critical Systems . .37 SCHOLAR PROFILES Tom Maniatis (1978): Mastering Methods and Exploring Molecular Mechanisms . 40 Bruce Stillman (1983): The Foundations of DNA Replication . .43 Luis Villarreal (1983): A Life in Viruses . .46 Gilbert Chu (1988): DNA Dreamer . .49 Jon Levine (1988): A Passion for Deciphering Pain . 52 Susan Dymecki (1999): Serotonin Circuit Master . 55 Hao Wu (2002): The Cellular Dimensions of Immunity . .58 Ajay Chawla (2003): Beyond Immunity . 61 Christopher Lima (2003): Structure Meets Function . 64 Laura Johnston (2004): How Life Shapes Up . .67 Senthil Muthuswamy (2004): Tackling Cancer in Three Dimensions . .70 David Sabatini (2004): Fueling Cell Growth . .73 David Tuveson (2004): Decoding a Cryptic Cancer . 76 Hilary Coller (2005): When Cells Sleep . .79 Diana Bautista (2010): An Itch for Knowledge . .82 David Prober (2010): Sleeping Like the Fishes . -
A Guide to the Archival Collection of the Robert Cook-Deegan Human
Bioethics Research Library The Joseph and Rose Kennedy Institute of Ethics bioethics.georgetown.edu A Guide to the Archival Collection of The Robert Cook-Deegan Human Genome Archive Set 2 April, 2013 Bioethics Research Library Joseph and Rose Kennedy Institute of Ethics Georgetown University Washington, D.C. Overview The Robert Cook-Deegan Human Genome Archive is founded on the bibliography of The Gene Wars: Science, Politics, and the Human Genome. The archive encompasses both physical and digital materials related to The Human Genome Project (HGP) and includes correspondence, government reports, background information, and oral histories from prominent participants in the project. Hosted by the Bioethics Research Library at Georgetown University the archive is comprised of 20.85 linear feet of materials currently and is expected to grow as new materials are processed and added to the collection. Most of the materials comprising the archive were obtained between the years 1986 and 1994. However, several of the documents are dated earlier. Introduction This box listing was created in order to assist the Bioethics Research Library in its digitization effort for the archive and is being shared as a resource to our patrons to assist in their use of the collection. The archive consists of 44 separate archive boxes broken down into three separate sets. Set one is comprised of nine boxes, set two is comprised of seven boxes, and set three is comprised of 28 boxes. Each set corresponds to a distinct addition to the collection in the order in which they were given to the library. No value should be placed on the importance of any given set, or the order the boxes are in, as each was accessed, processed, and kept in the order in which they were received. -
Molecular-Recognition-Directed Formation of Supramolecular Polymers
Polymer Journal (2013) 45, 363–383 & 2013 The Society of Polymer Science, Japan (SPSJ) All rights reserved 0032-3896/13 www.nature.com/pj INVITED REVIEW Molecular-recognition-directed formation of supramolecular polymers Takeharu Haino In recent years, significant research effort has focused on creating supramolecular polymers that can be attained by specific host–guest interactions of the repeating units. During the supramolecular polymerization process, molecular recognition events, which are predetermined by the molecular building blocks, are highly selective and directional for defining the size, direction and dimension of the resulting supramolecular polymers. The diversity of the supramolecular building blocks ranges from small aromatic units to macrocycles. Recently, the interplay of supramolecular and polymer chemistry has led to the creation of novel supramolecular materials, which display fascinating functions such as self-healing, stimuli-responsiveness and rubber-like elastomeric properties. Supramolecular cross-linking and supramolecular block copolymerization are the methods that have been used to install fascinating and functional moieties onto polymer backbones. Currently, the development of practical supramolecular polymeric materials is an ongoing challenge for supramolecular chemists. This review will focus on the recent developments in supramolecular polymers composed of discrete repeating units, as well as novel supramolecular materials produced by the interplay of supramolecular and polymer chemistry. Polymer Journal (2013) 45, 363–383; doi:10.1038/pj.2012.144; published online 1 August 2012 Keywords: block copolymerization; cross-linking; molecular recognition; noncovalent interaction; supramolecular chemistry; supramolecular polymer INTRODUCTION Liquid and molecular crystals lose polymeric structures and Synthetic polymers with tailored properties offer a wide range of properties in the isotropic state and in solution. -
Gene Pioneers: Donald Brown and Thomas Maniatis Win the 2012 Lasker~Koshland Special Achievement Award in Medical Science
Gene pioneers: Donald Brown and Thomas Maniatis win the 2012 Lasker~Koshland Special Achievement Award in Medical Science Kathryn Claiborn J Clin Invest. 2012;122(10):3383-3386. https://doi.org/10.1172/JCI66476. News The 2012 Lasker~Koshland Special Achievement Award in Medical Science recognizes Donald Brown (Carnegie Institute of Washington) and Thomas Maniatis (Columbia University) (Figure 1), two scientists whose career-long contributions were seminal to our understanding of what genes are and our ability to study and manipulate them, and whose commitment to mentorship have had tremendous impact on a generation of scientists. What is a gene? In the nineteenth century, an Austrian monk began a set of experiments in a small garden plot. Gregor Mendel’s detailed study of garden peas led him to understand that visible traits, such as the height or color of a plant, were determined by the combined inheritance of two physical particles from the two parent plants. Decades later, Theodor Boveri and Walter Sutton, analyzing meiotic cell divisions in grasshopper testes with the help of a microscope, hypothesized that Mendel’s hereditary factors — genes — could be carried on chromosomes. The groundwork was thus laid for a basic understanding of inheritance, but the question remained: what is a gene, exactly? Further understanding these entities — both their molecular makeup and their regulation — would require the dedication of innumerable scientific careers, as well as technical innovations that allowed the isolation and manipulation their sequences.Development -
Supramolecular Recognition: on the Kinetic Lability of Thermodynamically Stable Host–Guest Association Complexes
Supramolecular recognition: On the kinetic lability of thermodynamically stable host–guest association complexes Andrew J. Goshe*, Ian M. Steele*, Christopher Ceccarelli†, Arnold L. Rheingold†, and B. Bosnich*§ *Department of Chemistry, University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637; and †Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved January 16, 2002 (received for review November 2, 2001) A molecular receptor consisting of a spacer bearing two cofacially Table 1. Supramolecular assembly bonds disposed terpyridyl–palladium–ligand (terpy-Pd-L) units rigidly sepa- rated by about 7 Å has been investigated for molecular recognition of planar aromatic molecules. It is found that although the receptor forms stable 1:2 host–guest association complexes with 9-methylan- thracene (9-MA), the guest undergoes very rapid site exchange within the receptor and with external free 9-MA. A crystal structure of the 2:1 adduct shows one 9-MA in the molecular cleft defined by the two terpy-Pd-L units and the other resides on an outside face of one terpy-Pd-L unit. To establish the site residency time of the guests, a number of tethered molecules were prepared. These involve an anthracene molecule tethered to a pyridine ligand bound to the palladium atoms to form intramolecular host–guest adducts. Rotating-frame Overhauser effects were used to infer the site resi- many third row transition metal bonds are stable and nonlabile, dency of the anthracene guests in the receptor. Variable-temperature and such bonds are used as the permanent components of 1H NMR spectroscopy of the intramolecular host–guest complexes supramolecular structures.