Computational biology : a statistical mechanics perspective

301 Pages·2020·6.601 MB·English

by  Blossey, Ralf

Chapman & Hall/CRC
Computational biology has developed rapidly during the last two C Mathematical and Computational Biology Series
decades following the genomic revolution which culminated in the
o
sequencing of the human genome. More than ever it has developed
m
into a field which embraces computational methods from different
p
branches of the exact sciences: pure and applied mathematics,
u
computer science, theoretical physics. This Second Edition provides
t
a solid introduction to the techniques of statistical mechanics for
a
graduate students and researchers in computational biology and t
i
biophysics. o
n
• Material has been reorganized to clarify equilibrium and
a
nonequilibrium aspects of biomolecular systems
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• Content has been expanded, in particular in the treatment of the
B
electrostatic interactions of biomolecules and the application of
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non-equilibrium statistical mechanics to biomolecules o
• New network-based approaches for the study of proteins are l
o
presented.
g
All treated topics are put firmly in the context of the current research y
literature, allowing the reader to easily follow an individual path
S
into a specific research field. Exercises and Tasks accompany the
e
presentations of the topics with the intention of enabling the readers c
o
to test their comprehension of the developed basic concepts. n
d

Ralf Blossey is a Research Director at the French National Center E
d
for Scientific Research, the CNRS, and is based in Lille, in the North i
t
i
of France. His work during the last fifteen years has focused on the o
n
Computational Biology
application of statistical mechanics methods to DNA, proteins, gene
regulatory networks and chromatin. He has collaborated with many
scientists from computer science, mathematics, computational
A Statistical Mechanics Perspective
B
biology, molecular and cellular biology, as well as colleagues from
l
his original field of training, statistical physics. o
s Second Edition
s
e
y
COMPUTER SCIENCE & ENGINEERING
Ralf Blossey
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Computational Biology
A Statistical Mechanics
Perspective
Second Edition

Computational Biology
A Statistical Mechanics
Perspective
Second Edition
Ralf Blossey
CRCPress
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Library of Congress Cataloging-in-Publication Data
Names:Blossey,Ralf,author.
Title:Computationalbiology:astatisticalmechanicsperspective/
RalfBlossey.
Description:Secondedition.|BocaRaton,Florida:CRCPress,[2020]|
Series:Chapman&Hall/CRCmathematicalandcomputationalbiology|
Includesbibliographicalreferencesandindex.
Identifiers:LCCN2019011496|ISBN9781138587861(hbk:alk.paper)|
ISBN9780429503672(ebk)
Subjects:LCSH:Biomolecules--Mechanicalproperties.|Statistical
mechanics.|Computationalbiology.
Classification:LCCQH506.B572020|DDC572.80285--dc23
LCrecordavailableathttps://lccn.loc.gov/2019011496
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To SyMaNi and Mum

Contents
PREFACE TO THE SECOND EDITION ix
PREFACE TO THE FIRST EDITION xi
Part I Equilibrium Statistical Mechanics
Chapter 1(cid:4) Equilibrium Statistical Mechanics 3
1.1 Z: THE PARTITION FUNCTION 3
1.2 RELATION TO THERMODYNAMICS 7
1.3 COMPUTING Z 13
1.4 THE ISING MODEL 15
Chapter 2(cid:4) Biomolecular Structure: DNA, RNA, Proteins 39
2.1 DNA, RNA AND PROTEINS: THE BUILDING BLOCKS 39
2.2 REPRESENTING RNA STRUCTURE 47
2.3 COMPUTING RNA SECONDARY STRUCTURE:
COMBINATORICS 51
2.4 THE RNA PARTITION FUNCTION 55
2.5 PROTEIN FOLDING AND DOCKING 61
2.6 PULLING DNA 68
Chapter 3(cid:4) Phase Transitions in RNA and DNA 83
3.1 RNA PHASE BEHAVIOUR 83
3.2 THE DNA MELTING TRANSITION 86
3.3 THE MELTING PROFILES OF GENOMIC DNA AND
CDNA 98
vii
viii (cid:4) Contents
Chapter 4(cid:4) Soft Matter Electrostatics 119
4.1 THE FREE ENERGY OF ELECTROSTATIC SYSTEMS 119
4.2 THE POISSON-BOLTZMANN EQUATION 122
4.3 PROTEIN ELECTROSTATICS 126
4.4 CHROMATIN ELECTROSTATICS 131
Part II Non-equilibrium Statistical Mechanics
Chapter 5(cid:4) Back to P: Probabilities over Time 151
5.1 STOCHASTIC PROCESSES 152
5.2 THE MASTER EQUATION 155
5.3 THE FOKKER-PLANCK AND LANGEVIN EQUATIONS 163
5.4 SEQUENCEALIGNMENT:ANON-EQUILIBRIUMPHASE
TRANSITION 176
Chapter 6(cid:4) Fluctuation Theorems 191
6.1 THE FLUCTUATION-DISSIPATION THEOREM 191
6.2 THE JARZYNSKI EQUALITY AND CROOKS’
THEOREM 193
6.3 APPLICATIONS OF THE FLUCTUATION THEOREMS 195
Chapter 7(cid:4) Dynamics of Biological Networks 207
7.1 THE λ-REPRESSOR 208
7.2 DYNAMICS OF GENE REGULATORY NETWORKS 216
7.3 INTRINSIC NOISE 226
Chapter 8(cid:4) Biological Networks: Space 245
8.1 EXTRINSIC VS. INTRINSIC NOISE 245
8.2 THE TURING INSIGHT 249
8.3 NETWORKS AS GRAPHS 256
8.4 STATISTICAL MECHANICS OF NETWORKS 263
8.5 SMALL WORLDS 267
Index 281
Preface to the Second
Edition
I am grateful to the publisher who asked me to renew my book as a second
edition. Indeed, after more than ten years, the field of computational biol-
ogy/statistical physics—the particular interface of two fields I am interested
in—has matured in many ways. Going through the first edition again was a
great pleasure when comparing past views to current insights.
As a consequence, the book has substantially changed while maintaining its
corecontents.Newmaterialhasbeenadded,butinparticularIhavereworked
its whole architecture. In the second edition, there are only two parts: one on
equilibrium statistical physics and one on non-equilibrium statistical physics.
Thetheoreticaltoolsinthesefieldsthatthebookintroducesareplacedatthe
beginning of each part, and then the applications follow. I hope that this new
structure will help the readers to master the material.
As a side effect of following the now classic dichotomy of statistical physics—
equilibrium and non-equilibrium—the focus on universal aspects, those that
statistical physics is most attuned to, has been sharpened. Even more than
before, this makes the book not a biophysics book. Since 2006, when the first
edition went into print, new books on biophysics have appeared, especially
bioinformatics books.
I hope that with its modifications, including updated additional notes to the
literature and references, this book will continue to find its readership and
help to introduce its readers to this exciting field of research.
Lille, February 2019
Ralf Blossey
ix