Protein-Ligand Interactions: Methods and Applications PDF
Preview Protein-Ligand Interactions: Methods and Applications
Methods in Molecular Biology 1008 Mark A. Williams Tina Daviter Editors Protein-Ligand Interactions Methods and Applications Second Edition TM M E T H O D S I N M O L E C U L A R B I O L O G Y Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651 . Protein-Ligand Interactions Methods and Applications Second Edition Edited by Mark A. Williams and Tina Daviter ISMB Biophysics Centre Institute of Structural and Molecular Biology Birkbeck, University of London London, United Kingdom Editors Mark A. Williams Tina Daviter ISMB Biophysics Centre ISMB Biophysics Centre Institute of Structural and Molecular Biology Institute of Structural and Molecular Biology Birkbeck, University of London Birkbeck, University of London London, United Kingdom London, United Kingdom ISSN 1064-3745 ISSN 1940-6029 (electronic) ISBN 978-1-62703-397-8 ISBN 978-1-62703-398-5 (eBook) DOI 10.1007/978-1-62703-398-5 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013938157 # Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Humana Press is a brand of Springer Springer is part of Springer Science+Business Media (www.springer.com) Preface Proteins are the cell’s workers, their messengers and overseers. In these roles proteins specifically bind small molecules, nucleic acid and other protein partners. Cellular systems are closely regulated, and changes in the populations of particular protein complexes or products of protein-mediated reactions by as little as a factor of 2 can switch cells from one state to another, from growth to stasis, from replication to apoptosis. Such changes in populations correspond to very small effects on thermodynamics or kinetics of reactions. Consequently, detailed characterization of protein interactions is of paramount importance in a quantitative and integrative biology, which aims to understand biological systems in terms of their molecular components. Further, interfering with the interactions of proteins is the dominant strategy in the development of new pharmaceuticals. The discovery of novel small-molecule ligands, the characterization of their interactions with protein targets and the use of that information in guiding development of an inhibitor into a drug is a key component of the early stages of creating new medicines. This volume aims to provide a complete introduction to common and emerging procedures for characterizing the interactions of individual proteins. All stages of the research process are covered—from the initial discovery of natural substrates or potential drug leads to the detailed quantitative understanding of the mechanism of interaction. We focus on those techniques that are, or are anticipated to become, widely accessible; that are performable with mainstream commercial instrumentation. Much of this volume is aimed particularly at researchers new to the field of biophysical characterization of protein interactions—whether beginning graduate students or experts in allied areas of molecular cell biology, microbiology, pharmacology, medicinal chemistry or structural biology—who need to characterise their protein’s interactions in greater detail. There is a particular emphasis on obtaining good quality data and helping the researcher understand whether or not they have succeeded in doing so. We hope that the breadth of coverage and detailed consideration of technical issues will also serve as a reference for the professional molecular biophysicist “straying” outside their area of specific expertise. London, United Kingdom Mark A. Williams Tina Daviter v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix PART I INTRODUCTION AND OVERVIEW 1 Protein–Ligand Interactions: Fundamentals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Mark A. Williams 2 Protein Sample Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Tina Daviter and Re´mi Fronzes 3 Measurement of Protein–Ligand Complex Formation . . . . . . . . . . . . . . . . . . . . . 63 Peter N. Lowe, Cara K. Vaughan, and Tina Daviter PART II QUANTITATION OF THERMODYNAMICS AND KINETICS 4 Isothermal Titration Calorimetry for Studying Protein–Ligand Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 Luminita Damian 5 Rapid Mixing Kinetic Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Stephen R. Martin and Maria J. Schilstra 6 Protein–Ligand Interactions Using SPR Systems . . . . . . . . . . . . . . . . . . . . . . . . . . 139 A˚ sa Frostell, Lena Vinterba€ck, and Hans Sj¨obom PART III SPECTROSCOPIC METHODS 7 Fluorescence Techniques in Analysis of Protein–Ligand Interactions . . . . . . . . . 169 Gabor Mocz and Justin A. Ross 8 Circular and Linear Dichroism Spectroscopy for the Study of Protein–Ligand Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 Tina Daviter, Nikola Chmel, and Alison Rodger 9 Analyzing Protein–Ligand Interactions by Dynamic NMR Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 Anthony Mittermaier and Erick Meneses 10 Studying Metal Ion–Protein Interactions: Electronic Absorption, Circular Dichroism, and Electron Paramagnetic Resonance. . . . . . . . . . . . . . . . . 267 Liliana Quintanar and Lina Rivillas-Acevedo 11 Monitoring Protein–Ligand Interactions by Time-Resolved FTIR Difference Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 Carsten K¨otting and Klaus Gerwert vii viii Contents PART IV LIGAND DISCOVERY 12 Biophysical Methods in Drug Discovery from Small Molecule to Pharmaceutical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 Geoffrey Holdgate, Stefan Geschwindner, Alex Breeze, Gareth Davies, Nicola Colclough, David Temesi, and Lara Ward 13 Biophysical Screening for the Discovery of Small-Molecule Ligands . . . . . . . . . 357 Alessio Ciulli 14 Screening Protein–Small Molecule Interactions by NMR. . . . . . . . . . . . . . . . . . . 389 Ben Davis PART V MOLECULES IN NATIVE ENVIRONMENTS 15 Model Membrane Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417 Heiko Keller, Remigiusz Worch, and Petra Schwille 16 Quantitative Fluorescence Co-localization to Study Protein–Receptor Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439 Shanica N. Pompey, Peter Michaely, and Katherine Luby-Phelps PART VI STRUCTURAL AND COMPUTATIONAL METHODS 17 Studying Protein–Ligand Interactions Using X-Ray Crystallography. . . . . . . . . 457 Andrew P. Turnbull and Paul Emsley 18 Molecular Fields in Ligand Discovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 Paul J. Gane and A.W. Edith Chan 19 Structure-Based Virtual Screening for Novel Ligands . . . . . . . . . . . . . . . . . . . . . . 501 William R. Pitt, Mark D. Calmiano, Boris Kroeplien, Richard D. Taylor, James P. Turner, and Michael A. King Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521 Contributors ALEX BREEZE AstraZeneca R&D, Macclesfield, UK MARK D. CALMIANO Department of Medicinal Chemistry, UCB Pharma, Slough, UK A.W. EDITH CHAN Medicinal Chemistry, Wolfson Institute for Biomedical Research, University College London, London, UK NIKOLA CHMEL Department of Chemistry, University of Warwick, Coventry, UK; Warwick Centre for Analytical Science, University of Warwick, Coventry, UK ALESSIO CIULLI College of Life Sciences, University of Dundee, Division of Biological Chemistry and Drug Discovery, The Wellcome Trust Biocentre, Scotland, UK; Department of Chemistry, University of Cambridge, Cambridge, UK NICOLA COLCLOUGH AstraZeneca R&D, Macclesfield, UK LUMINITA DAMIAN Microcal Products, GE Healthcare, Little Chalfont, UK GARETH DAVIES AstraZeneca R&D, Macclesfield, UK BEN DAVIS Vernalis Ltd (R&D), Great Abington, Cambridge, UK TINA DAVITER ISMB Biophysics Centre, Institute of Structural and Molecular Biology, Birkbeck, University of London, London, UK PAUL EMSLEY Structural Studies, MRC Laboratory of Molecular Biology, Cambridge, UK RE´MI FRONZES Unite´ G5 Biologie structurale de la se´cre´tion bacte´rienne, Institut Pasteur, Paris, France A˚ SA FROSTELL GE Healthcare Bio-Sciences AB, Uppsala, Sweden PAUL J. GANE Medicinal Chemistry, Wolfson Institute for Biomedical Research, University College London, London, UK KLAUS GERWERT Lehrstuhl fu€r Biophysik, Ruhr-Universita€t Bochum, Bochum, Germany STEFAN GESCHWINDNER AstraZeneca R&D, Mo¨lndal, Sweden GEOFFREY HOLDGATE AstraZeneca R&D, Macclesfield, UK HEIKO KELLER BIOTEC, Dresden University of Technology, Dresden, Germany MICHAEL A. KING Department of Medicinal Chemistry, UCB Pharma, Slough, UK CARSTEN KO¨ TTING Lehrstuhl fu€r Biophysik, Ruhr-Universita€t Bochum, Bochum, Germany BORIS KROEPLIEN Department of Medicinal Chemistry, UCB Pharma, Slough, UK PETER N. LOWE Biomolecular Interactions Consultancy, Hertford, UK KATHERINE LUBY-PHELPS Department of Cell Biology, UT Southwestern Medical School, Dallas, TX, USA STEPHEN R. MARTIN Division of Physical Biochemistry, MRC National Institute for Medical Research, London, UK ERICK MENESES Department of Chemistry, McGill University, Montreal, QC, Canada PETER MICHAELY Department of Cell Biology, UT Southwestern Medical School, Dallas, TX, USA ANTHONY MITTERMAIER Department of Chemistry, McGill University, Montreal, QC, Canada ix
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