An Introduction to Computational Biochemistry - C. Tsai (2002) WW

371 Pages·2002·6.69 MB·English

AN INTRODUCTION TO
COMPUTATIONAL
BIOCHEMISTRY

AN INTRODUCTION TO
COMPUTATIONAL
BIOCHEMISTRY

C. Stan Tsai, Ph.D.
Department of Chemistry
and Institute of Biochemistry
Carleton University
Ottawa, Ontario, Canada

A JOHN WILEY & SONS, INC., PUBLICATION

This book is printed on acid-free paper. �

Copyright � 2002 by Wiley-Liss, Inc., New York. All rights reserved.

Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Tsai, C. Stan.
An introduction to computational biochemistry / C. Stan Tsai.
p. cm.
Includes bibliographical references and index.
ISBN 0-471-40120-X (pbk. : alk. paper)
1. Biochemistry--Data processing. 2. Biochemistry--Computer simulation. 3.
Biochemistry--Mathematics. I. Title.

QP517.M3 T733 2002
572�.0285--dc21
2001057366

Printed in the United States of America.

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a

CONTENTS

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ix

1 INTRODUCTION
1

1.1. Biochemistry: Studies of Life at the Molecular Level . . . . . . . . .
1
1.2. Computer Science and Computational Sciences . . . . . . . . . . . . .
5
1.3. Computational Biochemistry: Application of Computer
Technology to Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9

2 BIOCHEMICAL DATA: ANALYSIS AND
MANAGEMENT
11

2.1. Statistical Analysis of Biochemical Data
. . . . . . . . . . . . . . . . . .
11
2.2. Biochemical Data Analysis with Spreadsheet Application . . . . .
20
2.3. Biochemical Data Management with Database Program . . . . . .
28
2.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
31
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
40

3 BIOCHEMICAL EXPLORATION: INTERNET RESOURCES
41

3.1. Introduction to Internet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41
3.2. Internet Resources of Biochemical Interest . . . . . . . . . . . . . . . . .
46
3.3. Database Retrieval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
48
3.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
52
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
52

4 MOLECULAR GRAPHICS: VISUALIZATION OF
BIOMOLECULES
53

4.1. Introduction to Computer Graphics
. . . . . . . . . . . . . . . . . . . . .
53
4.2. Representation of Molecular Structures . . . . . . . . . . . . . . . . . . .
56
4.3. Drawing and Display of Molecular Structures . . . . . . . . . . . . . .
60
4.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
69
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
70
v

5 BIOCHEMICAL COMPOUNDS: STRUCTURE AND
ANALYSIS
73

5.1. Survey of Biomolecules
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
73
5.2. Characterization of Biomolecular Structures . . . . . . . . . . . . . . .
80
5.3. Fitting and Search of Biomolecular Data and Information . . . .
87
5.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
98
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
103

6 DYNAMIC BIOCHEMISTRY: BIOMOLECULAR
INTERACTIONS
107

6.1. Biomacromolecule—Ligand Interactions . . . . . . . . . . . . . . . . . . .
107
6.2. Receptor Biochemistry and Signal Transduction . . . . . . . . . . . .
111
6.3. Fitting of Binding Data and Search for Receptor Databases . . .
113
6.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
119
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
121

7 DYNAMIC BIOCHEMISTRY: ENZYME KINETICS
123

7.1. Characterization of Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . .
123
7.2. Kinetics of Enzymatic Reactions . . . . . . . . . . . . . . . . . . . . . . . .
126
7.3. Search and Analysis of Enzyme Data . . . . . . . . . . . . . . . . . . . . .
133
7.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
140
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
144

8 DYNAMIC BIOCHEMISTRY: METABOLIC SIMULATION
147

8.1. Introduction to Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . .
147
8.2. Metabolic Control Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . .
152
8.3. Metabolic Databases and Simulation . . . . . . . . . . . . . . . . . . . . .
153
8.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
160
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
162

9 GENOMICS: NUCLEOTIDE SEQUENCES AND
RECOMBINANT DNA
165

9.1. Genome, DNA Sequence, and Transmission of Genetic
Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
165
9.2. Recombinant DNA Technology . . . . . . . . . . . . . . . . . . . . . . . . .
169
9.3. Nucleotide Sequence Analysis
. . . . . . . . . . . . . . . . . . . . . . . . . .
171
9.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
179
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
181

vi
CONTENTS

10 GENOMICS: GENE IDENTIFICATION
183

10.1. Genome Information and Features
. . . . . . . . . . . . . . . . . . . . .
183
10.2. Approaches to Gene Identification . . . . . . . . . . . . . . . . . . . . . .
185
10.3. Gene Identification with Internet Resources . . . . . . . . . . . . . . .
188
10.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
204
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
207

11 PROTEOMICS: PROTEIN SEQUENCE ANALYSIS
209

11.1. Protein Sequence: Information and Features . . . . . . . . . . . . . .
209
11.2. Database Search and Sequence Alignment . . . . . . . . . . . . . . . .
213
11.3. Proteomic Analysis Using Internet Resources:
Sequence and Alignment . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
221
11.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
228
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
230

12 PROTEOMICS: PREDICTION OF PROTEIN STRUCTURES
233

12.1. Prediction of Protein Secondary Structures from Sequences . .
233
12.2. Protein Folding Problems and Functional Sites . . . . . . . . . . . .
236
12.3. Proteomic Analysis Using Internet Resources: Structure
and Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
243
12.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
264
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
266

13 PHYLOGENETIC ANALYSIS
269

13.1. Elements of Phylogeny . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
269
13.2. Methods of Phylogenetic Analysis . . . . . . . . . . . . . . . . . . . . . .
271
13.3. Application of Sequence Analyses in Phylogenetic Inference . .
275
13.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
280
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
284

14 MOLECULAR MODELING: MOLECULAR MECHANICS
285

14.1. Introduction to Molecular Modeling . . . . . . . . . . . . . . . . . . . .
285
14.2. Energy Minimization, Dynamics Simulation, and
Conformational Search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
287
14.3. Computational Application of Molecular Modeling Packages .
296
14.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
311
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
313

15 MOLECULAR MODELING: PROTEIN MODELING
315

15.1. Structure Similarity and Overlap . . . . . . . . . . . . . . . . . . . . . . .
315
15.2. Structure Prediction and Molecular Docking . . . . . . . . . . . . . .
319

CONTENTS
vii

15.3. Applications of Protein Modeling
. . . . . . . . . . . . . . . . . . . . . .
322
15.4. Workshops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
337
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
340

APPENDIX
343

1. List of Software Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
343
2. List of World Wide Web Servers . . . . . . . . . . . . . . . . . . . . . . . . .
345
3. Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
353

INDEX
357

viii
CONTENTS

PREFACE

Since the arrival of information technology, biochemistry has evolved from an
interdisciplinary role to becoming a core program for a new generation of interdis-
ciplinary courses such as bioinformatics and computational biochemistry. A demand
exists for an introductory text presenting a unified approach for the combined
subjects that meets the need of undergraduate science and biomedical students.
This textbook is the introductory courseware at an entry level to teach students
biochemical principles as well as the skill of using application programs for
acquisition, analysis, and management of biochemical data with microcomputers.
The book is written for end users, not for programmers. The objective is to raise the
students’ awareness of the applicability of microcomputers in biochemistry and to
increase their interest in the subject matter. The target audiences are undergraduate
chemistry, biochemistry, biomedical sciences, molecular biology, and biotechnology
students or new graduate students of the above-mentioned fields.
Every field of computational sciences including computational biochemistry is
evolving at such a rate that any book can seem obsolete if it has to discuss the
technology. For this reason, this text focuses on a conceptual and introductory
description of computational biochemistry. The book is neither a collection of
presentations of important computational software packages in biochemistry nor the
exaltation of some specific programs described in more detail than others. The
author has focused on the description of specific software programs that have been
used in his classroom. This does not mean that these programs are superior to
others. Rather, this text merely attempts to introduce the undergraduate students in
biochemistry, molecular biology, biotechnology, or chemistry to the realm of
computer methods in biochemical teaching and research. The methods are not
alternatives to the current methodologies, but are complementary.
This text is not intended as a technical handbook. In an area where the speed
of change and growth is unusually high, a book in print cannot be either compre-
hensive or entirely current. This book is conceived as a textbook for students who
have taken biochemistry and are familiar with the general topics. However, the book
aims to reinforce subject matter by first reviewing the fundamental concepts of
biochemistry briefly. These are followed by overviews on computational approaches
to solve biochemical problems of general and special topics.
This book delves into practical solutions to biochemical problems with software
programs and interactive bioinformatics found on the World Wide Web. After the
introduction in Chapter 1, the concept of biochemical data analysis and management
is described in Chapter 2. The interactions between biochemists and computers are
ix

the topics of Chapter 3 (Internet resources) and Chapter 4 (computer graphics).
Computational applications in structural biochemistry are described in Chapter 5
(biochemical compounds) and then in Chapters 14 and 15 (molecular modeling).
Dynamic biochemistry is treated in Chapter 6 (biomolecular interactions), Chapter
7 (enzyme kinetics), and Chapter 8 (metabolic simulation). Information biochemistry
that overlaps bioinformatics and utilizes the Internet resources extensively is dis-
cussed in Chapters 9 and 10 (genomics), Chapters 11 and 12 (proteomics), and
Chapter 13 (phylogenetic analysis).
I would like to thank all the authors who elucidate sequences and 3D structures
of nucleic acids as well as proteins, and they kindly place such valuable information
in the public domain. The contributions of all the authors who develop algorithms
for free access on the Web sites and who provide highly useful software programs
for free distribution are gratefully acknowledged. I thank them for granting me the
permissions to reproduce their web pages, online and e-mail returns. I am grateful
to Drs. Athel Cornish-Bowden (Leonora), Tom Hall (BioEdit), Petr Kuzmic
(DynaFit), and Pedro Mendes (Gepasi) for the consents to use their software
programs. The effort of all the developers and managers of the many outstanding
Web sites are most appreciated. The development of this text would not have been
possible without the contribution and generosity of these investigators, authors, and
developers. I am thankful to Dr. D. R. Wiles for reading parts of this manuscript. It
is my pleasure to state that the writing of this text has been a family effort. My wife,
Alice, has been most instrumental in helping me complete this text by introducing
and continuously coaching me on the wonderful world of microcomputers. My son,
Willis, and my daughter, Ellie, have assisted me in various stages of this endeavor.
The credit for the realization of this textbook goes to Luna Han, Editor, and
Danielle Lacourciere, Associate Managing Editor, of John Wiley & Sons. This book
is dedicated to Alice.

C. Stan Tsai
Ottawa, Ontario, Canada

x
PREFACE