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Protein Folding Protocols 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™ METHODS IN MOLECULAR BIOLOGY™ 350 ProteinProtein FoldingFolding ProtocolsProtocols Edited by Yawen Bai Ruth Nussinov Protein Folding Protocols 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™ John M. Walker, SERIES EDITOR 380. Immunological Tolerance: Methods and Protocols, 357. Cardiovascular Proteomics: Methods and Protocols, edited by Paul J. Fairchild, 2007 edited by Fernando Vivanco, 2006 379. Glycovirology Protocols, edited by Richard J. 356. High-Content Screening: A Powerful Approach Sugrue, 2007 to Systems Cell Biology and Drug Discovery, 378. Monoclonal Antibodies: Methods and Protocols, edited by Ken Guiliano, D. Lansing Taylor, edited by Maher Albitar, 2007 and Jeffrey Haskins, 2007 377. Microarray Data Analysis: Methods and 355. Plant Proteomics: Methods and Protocols, edited Applications, edited by Michael J. 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PRINS and In Situ PCR Protocols, Second Wolfram Weckwerth, 2007 Edition, edited by Franck Pellestor, 2006 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™ Protein Folding Protocols Edited by Yawen Bai Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD and Ruth Nussinov Center for Cancer Research Nanobiology Program SAIC, National Cancer Institute-Frederick, Frederick, MD and Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel © 2007 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. Methods in Molecular BiologyTM is a trademark of The Humana Press Inc. All papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. This publication is printed on acid-free paper. ∞ ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials. Cover illustration: Figure 3 from Chapter 15, "Intermediates and Transition States in Protein Folding," by D. Thirumalai and Dmitri K. Klimov. Production Editor: Erika J. Wasenda Cover design by Patricia F. Cleary For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-834; E-mail: [email protected]; or visit our Website: www.humanapress.com Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $30.00 per copy is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [1-58829-622-9/07 $30.00]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 eISBN:1-59745-189-4 ISSN:1064-3745 Library of Congress Cataloging in Publication Data Protein folding protocols / edited by Yawen Bai and Ruth Nussinov. p. ; cm. -- (Methods in molecular biology ; 350) Includes bibliographical references and index. ISBN 1-58829-622-9 (alk. paper) 1. Protein folding. 2. Proteins--Conformation. 3. Proteins--Analysis. [DNLM: 1. Protein Folding. 2. Protein Conformation. 3. Proteins--analysis. QU 55 P96635 2006] I. Bai, Yawen. II. Nussinov, Ruth. III. Series: Methods in molecular biology (Clifton, N.J.) ; 350. QP551.P695822 2006 572'.633--dc22 2006002791 Preface Protein Folding Protocols presents protocols for studying and characterizing steps and conformational ensembles populating pathways in protein folding from the unfolded to the folded state. It further presents a sample of approaches toward the prediction of protein structure starting from the amino acid sequence, in the absence of overall homologous sequences. Protein folding is a crucial step in the transfer of genetic information from the DNA to the protein. The Genome Project has led to a huge number of available DNA sequences and, therefore, protein sequences. The Structural Genomics initiative largely aims to obtain “new” folds not currently present in the Protein Data Bank. Yet, the number of available structures inevitably lags behind the number of sequences. At the same time, an equally important problem is to find out the types and scope of dissimilar (nonhomologous) protein sequences that adopt a similar fold. Assembling data and comprehension of the sequence space of protein folds should be very useful in computational protein structure prediction. This would enhance the scope of homology modeling, which currently is the method of choice. Thus, experimental and theoretical studies on the relationship between sequence and structure are critical. Figuring out the relationship between sequence and structure would further assist in the prediction of fibril structures observed in protein misfolding diseases, and in figuring out the conformational changes and dynamics resulting from mutations. Protein folding is one of the most important and challenging problems in current molecular and chemical biology. This book reviews some of the recently developed methods for studying protein folding. The starting point of a folding process is the unfolded state. Eliezer describes how some of the local structural properties of the unfolded state may be charac- terized using multidimensional nuclear magnetic resonance (NMR). Gebel and Shortle review how the global structures of the unfolded state may
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