introduces :


Tamar Schlick
Molecular Modeling and Simulation - An Interdisciplinary Guide.
Springer, New York, 2002
ISBN    0-387-95404-X
EUR 85.00      about $85.00

From the book cover, rear:

        
         
        INTERDISCIPLINARY APPLIED MATHEMATICS
              MATHEMATICAL BIOLOGY

       


  

    
This book evolved from an interdisciplinary graduate course entitled
Molecular Modeling developed at New York University. Its primary goal
is to stimulate excitement for molecular modeling research while pro-
viding grounding in the discipline. Other scientists who wish to enter,
or become familiar with, the field of biomolecular modeling and Simu-
lation may also benefit from the broad coverage of problems and
approaches. 
The book surveys three broad topics: (a) biomolecular structure and
modeling—current problems and state of computations; (b) molecular
mechanics—force field origin, composition, and evaluation tech-
niques; and (c) simulation techniques—conformational sampling by 
geometry optimization, Monte Carlo, and molecular dynamics
approaches. 
 
    

  

Appendices featuring homework assignments,
reading lists, and other information useful for teaching molecular modeling complement the
material in the main text.
         
Tamar Schlick is Professor of Chemistry, Mathematics, and Computer Science at New York
University. Since her graduate work in Applied Mathematics at Courant Institute, NYU,
her group
has been working in the area of biomolecular simulations, both in algorithm development and
in applications to nucleic-acid structure and regulatory protein/DNA processes.

------------------

"The interdisciplinary structural biology community has waited long for a book of this kind
which provides an excellent introduction to molecular modeling. In a very readable approach,
the student is led easily through the underlying computational methodology involving force
fields and simulation protocols."         
                              —Harald A. Scheraga, Todd Professor of Chemistry Emeritus, 
                               Cornell University, Ithaca, NY, USA
         
"A uniquely valuable introduction to the modeling of biomolecular structure and dynamics. A
rigorous and up-to-date treatment of the foundations, enlivened by engaging anecdotes and historical notes."
                              —J. Andrew McCammon, HHMI, 
                              University of California at San Diego, USA
         
"I am often asked by physicists, mathematicians and engineers to recommend a book that would
be useful to get them started in computational molecular biology. I am also often approached
by my colleagues in computational biology to recommend a solid textbook for a graduate course
in the area. Schlick has written the book that I will be recommending to both groups. She has
done an amazing job in writing a book that is both suitably accessible for beginners, and suitably rigorous for experts."
                               — J.J. Collins, Co-Director, Professor of Biomedical
                                 Engineering, Boston University, USA

Contents:

1.1 A Multidisciplinary Enterprise
      1.1.1 Consilience
      1.1.2 What is Molecular Modeling
      1.1.3 Need For Critical Assessment
      1.1.4 Text Overview
1.2 Molecular Mechanics
      1.2.1 Pioneers
      1.2.2 Simulation Perspective
1.3 Experimental Progress
      1.3.1 Protein Crystallography
      1.3.2 DNA Structure
      1.3.3 Crystallography
      1.3.4 NMR Spectroscopy
1.4 Modern Era
      1.4.1 Biotechnology
      1.4.2 PCR and Beyond
1.5 Genome Sequencing
      1.5.1 Sequencing Overview
      1.5.2 Human Genome
Chapter 1 References (Postscript)   (PDF)
  
2 Biomolecular Structure and Modeling: Problem and Application Perspective 
 2.1 Computational Challenges
      2.1.1 Bioinformatics
      2.1.2 Structure From Sequence
2.2 Protein Folding
      2.2.1 Folding Views
      2.2.2 Folding Challenges
      2.2.3 Folding Simulations
      2.2.4 Chaperones
      2.2.5 Unstructured Proteins
2.3 Protein Misfolding
      2.3.1 Prions 
      2.3.2 Infectious Proteins?
      2.3.3 Hypotheses 
      2.3.4 Other Misfolding Processes
      2.3.5 Function From Structure
2.4 Practical Applications
      2.4.1 Drug Design
      2.4.2 AIDS Drugs
      2.4.3 Other Drugs
      2.4.4 A Long Way To Go 
      2.4.5 Better Genes
      2.4.6 Designer Foods
      2.4.7 Designer Materials
      2.4.8 Cosmeceuticals
  
3 Protein Basic 
 3.1 The Machinery of Life
      3.1.1 From Tissues to Hormones
      3.1.2 Size and Function Variability
      3.1.3 Chapter Overview
3.2 The Amino Acid Building Blocks
      3.2.1 Basic C Unit
      3.2.2 Essential and Nonessential Amino Acids
      3.2.3 Linking Amino Acids
      3.2.4 The Amino Acid Repertoire
3.3 Sequence Variations in Proteins
      3.3.1 Globular Proteins
      3.3.2 Membrane and Fibrous Proteins
      3.3.3 Emerging Patterns from Genome Databases
      3.3.4 Sequence Similarity
3.4 Protein Conformation Framework
      3.4.1 The Flexible phi and psi and Rigid omega Dihedral Angles
      3.4.2 Rotameric Structures
      3.4.3 Ramachandran Plots
      3.4.4 Conformational Hierarchy
  
4 Protein Hierarchy 
 4.1 Structure Hierarchy
4.2 Helices: A Common Secondary Structural Element
      4.2.1 Classic  - Helix
      4.2.2 310 and  Helices
      4.2.3 Left - Handed  - Helix
      4.2.4 Collagen Helix
4.3  - Sheets: A Common Secondary Structural Element
4.4 Turns and Loops 
4.5 Formation of Supersecondary and Tertiary Structure
      4.5.1 Complex 3D Networks
      4.5.2 Classes in Protein Architecture
      4.5.3 Classes are Further Divided into Folds
4.6  - Class Folds
      4.6.1 Bundles
      4.6.2 Folded Leafs
      4.6.3 Hairpin Arrays
4.7  - Class Folds
      4.7.1 Anti - Parallel  Domains
      4.7.2 Parallel and Antiparallel Combinations
4.8  /  and  +  - Class Folds
      4.8.1  /  Barrels
      4.8.2 Open Twisted  /  Folds
      4.8.3 Leucine-Rich  /  Folds
      4.8.4  +  Folds
4.9 Number of Folds
      4.9.1 Finite Number?
      4.9.2 Concerted Target Selection: Structural Genomics
4.10 Quaternary Structure
      4.10.1 Viruses
      4.10.2 From Ribosomes to Dynamic Networks
4.11 Structure Classification
  
5 Nucleic Acids Structure 
 5.1 DNA, Life's Blueprint
      5.1.1 The Kindled Field of Molecular Biology
      5.1.2 DNA Processes
      5.1.3 Challenges in Nucleic Acid Structure
      5.1.4 Chapter Overview
5.2 The Basic Building Blocks of Nucleic Acids
      5.2.1 Nitrogenous Bases
      5.2.2 Hydrogen Bonds
      5.2.3 Nucleotides
      5.2.4 Polynucleotides
      5.2.5 Stabilizing Polynucleotide Interactions
      5.2.6 Chain Notation
      5.2.7 Atomic Labeling
      5.2.8 Torsion Angle Labeling 
5.3 Nucleic Acid Conformational Flexibility
      5.3.1 The Furanose Ring
      5.3.2 Backbone Torsional Flexibility
      5.3.3 The Glycosyl Rotation
      5.3.4 Sugar/Glycosyl Combinations
      5.3.5 Basic Helical Descriptors
      5.3.6 Base - Pair Parameters
5.4 Canonical DNA Forms
      5.4.1 B-DNA
      5.4.2 A-DNA
      5.4.3 Z-DNA
      5.4.4 Comparative Features
  
6 Topics in Nucleic Acids Structure 
 6.1 Introduction
6.2 DNA Sequence Effects
      6.2.1 Local Deformations
      6.2.2 Orientation Preferences in Dinucleotide Steps
      6.2.3 Intrinsic DNA Bending in A-Tracts
      6.2.4 Sequence Deformability Analysis Continues
6.3 DNA Hydration and Ion Interactions
      6.3.1 Resolution Difficulties
      6.3.2 Basic Patterns
6.4 DNA/Protein Interactions
      Supplement to section 6.4 (Postscript)   (PDF) 
6.5 Variations on a Theme
      6.5.1 Hydrogen Bonding Patterns in Polynucleotides
      6.5.2 Hybrid Helical/Nonhelical Forms 
      6.5.3 Overstretched and Understretched DNA
6.6 RNA Structure
      6.6.1 RNA Chains Fold Upon Themselves
      6.6.2 RNA's Diversity
      6.6.3 RNA at Atomic Resolution
      6.6.4 Emerging Themes in RNA Structure and Folding
6.7 Cellular Organization of DNA
      6.7.1 Compaction of Genomic DNA 
      6.7.2 Coiling of the DNA Helix Itself
      6.7.3 Chromosomal Packaging of Coiled DNA 
6.8 Mathematical Characterization of DNA Supercoiling
      6.8.1 DNA Topology and Geometry
6.9 Computational Treatments of DNA Supercoiling 
      6.9.1 DNA as a Flexible Polymer
      6.9.2 Elasticity Theory Framework
      6.9.3 Simulations of DNA Supercoiling
  
7 Theoretical Approaches 
 7.1 The Merging of Theory and Experiment
      7.1.1 Exciting Times for Computationalists!
      7.1.2 The Future of Biocomputations
      7.1.3 Chapter Overview
7.2 QM Foundations
      7.2.1 The Schrodinger Wave Equation
      7.2.2 The Born-Oppenheimer Approximation
      7.2.3 Ab Initio
      7.2.4 Semi-Empirical QM
      7.2.5 Recent Advances in Quantum Mechanics 
      7.2.6 From Quantum to Molecular Mechanics
7.3 Molecular Mechanics Principles
      7.3.1 The Thermodynamic Hypothesis
      7.3.2 Additivity
      7.3.3 Transferability
7.4 Molecular Mechanics Formulation
      7.4.1 Configuration Space
      7.4.2 Functional Form
      7.4.3 Some Current Limitations
  
8 Force Fields 
 8.1 Formulation of the Model and Energy
8.2 Normal Modes
      8.2.1 Characteristic Motions
      8.2.2 Spectra of Biomolecules
      8.2.3 Spectra As Force Constant Sources
      8.2.4 In-Plane and Out-of-Plane Bending
8.3 Bond Length Potentials
      8.3.1 Harmonic Term
      8.3.2 Morse Term
      8.3.3 Cubic and Quartic Term
8.4 Bond Angle Potentials
      8.4.1 Harmonic and Trigonometric Terms
      8.4.2 Cross Bond Stretch / Angle Bend Terms
8.5 Torsional Potentials
      8.5.1 Origin of Rotational Barriers
      8.5.2 Fourier Terms
      8.5.3 Torsional Parameter Assignment
      8.5.4 Improper Torsion
      8.5.5 Cross Dihedral/Bond Angle and Improper/Improper Dihedral Terms
8.6 The van der Waals Potential
      8.6.1 Rapidly Decaying Potential
      8.6.2 Parameter Fitting From Experiment
      8.6.3 Two Parameter Calculation Protocols
8.7 The Coulombic Potential
      8.7.1 Coulomb's Law: Slowly Decaying Potential
      8.7.2 Dielectric Function
      8.7.3 Partial Charges
8.8 Parameterization
      8.8.1 A Package Deal
      8.8.2 Force Field Performance
  
9 Nonbonded Computations  
 9.1 A Computational Bottleneck
9.2 Approaches for Reducing Computational Cost
      9.2.1 Simple Cutoff Schemes
      9.2.2 Ewald and Multipole Schemes
9.3 Spherical Cutoff Techniques
      9.3.1 Technique Categories
      9.3.2 Guidelines for Cutoff Functions
      9.3.3 General Cutoff Formulations
      9.3.4 Potential Switch
      9.3.5 Force Switch
      9.3.6 Shift Functions
9.4 The Ewald Method
      9.4.1 Periodic Boundary Conditions
      9.4.2 Ewald Sum and Crystallography
      9.4.3 Morphing a Conditionally Convergent Sum
      9.4.4 Finite-Dielectric Correction
      9.4.5 Ewald Sum Complexity
      9.4.6 Resulting Ewald Summation
      9.4.7 Practical Implementation
9.5 The Multipole Method
      9.5.1 Basic Hierarchical Strategy
      9.5.2 Historical Perspective
      9.5.3 Expansion in Spherical Coordinates
      9.5.4 Biomolecular Implementations
      9.5.5 New Variants
9.6 Continuum Solvation
      9.6.1 Need for Simplification!
      9.6.2 Potential of Mean Force
      9.6.3 Stochastic Dynamics
      9.6.4 Continuum Electrostatics
  
10  Multivariate Minimization  
 10.1 Optimization Applications
      10.1.1 Algorithmic Understanding Needed
      10.1.2 Chapter Overview
10.2 Fundamentals
      10.2.1 Problem Formulation
      10.2.2 Independent Variables
      10.2.3 Function Characteristics
      10.2.4 Local and Global Minima
      10.2.5 Derivatives
      10.2.6 Hessian Matrix
10.3 Basic Algorithms
      10.3.1 Greedy Descent
      10.3.2 Line Searches
      10.3.3 Trust Region Methods
      10.3.4 Convergence Criteria
10.4 Newton's Method
      10.4.1 Newton in One Dimension
      10.4.2 Newton's Method for Minimization
      10.4.3 Multivariate Newton
10.5 Large-Scale methods
      10.5.1 Quasi-Newton (QN)
      10.5.2 Conjugate Gradient (CG)
      10.5.3 Truncated-Newton (TN)
      10.5.4 Simple Example
10.6 Software
      10.6.1 Popular Newton and CG
      10.6.2 CHARMM's ABNR
      10.6.3 CHARMM's TN
      10.6.4 Comparative Performance on Molecular Systems
10.7 Recommendations
10.8 Future Outlook
  
11 Monte Carlo Techniques  
 11.1 Monte Carlo Popularity
      11.1.1 A Winning Combination
      11.1.2 From Needles to Bombs
      11.1.3 Chapter Overview
      11.1.4 Importance of Error Bars
11.2 Random Number Generators
      11.2.1 What is Random?
      11.2.2 Properties of Generators?
      11.2.3 Linear Congruential Generators
      11.2.4 Other Generators
      11.2.5 Artifacts Generators
      11.2.6 Recommendations
11.3 Gaussian Random Variates 
      11.3.1 Manipulation of Uniform Random Variables
      11.3.2 Normal Variates in Molecular Simulations
      11.3.3 Odeh and Evans Method
      11.3.4 Box/Muller Method
11.4 Means for Monte Carlo Sampling 
      11.4.1 Expected Values
      11.4.2 Error Bars
      11.4.3 Batch Means
11.5 Monte Carlo Sampling
      11.5.1 Probability Density Function
      11.5.2 Equilibrium or Dynamics
      11.5.3 Ensembles
      11.5.4 Importance Sampling
11.6 Hybrid MC
      11.6.1 MC and MD
      11.6.2 Basic Idea
      11.6.3 Variants and Other Hybrid Approaches
  
12  Molecular Dynamics: Basics  (Postscript)  (PDF)
 
 12.1 Introduction
      12.1.1 Why Molecular Dynamics?
      12.1.2 Background
      12.1.3 MD Chapters Outline
12.2 Laplace's Vision of Newtonian Mechanics
      12.2.1 The Dream
      12.2.2 Deterministic Mechanics
      12.2.3 Neglect of Electronic Motion
      12.2.4 Deterministic Mechanics
      12.2.5 Neglect of Electronic Motion
12.3 Basics
      12.3.1 Following Motion
      12.3.2 Trajectory Quality
      12.3.3 System Setting
      12.3.4 Trajectory Sensitivity
      12.3.5 Simulation Protocol
      12.3.6 High-Speed Implementations
      12.3.7 Analysis and Visualization
      12.3.8 Reliable Numerical Integration
      12.3.9 Computational Complexity
12.4 The Verlet Algorithm
      12.4.1 Position and Velocity Propagation
      12.4.2 Leapfrog, Velocity Verlet, and Position Verlet
12.5 Constrained Dynamics
12.6 Various MD Ensembles
      12.6.1 Ensemble Types
      12.6.2 Simple Algorithms
      12.6.3 Extended System Methods
Chapter 12 References   (Postscript)   (PDF)
  
13  Molecular Dynamics: Further Topics  
 13.1 Introduction
13.2 Symplectic Integrators
      13.2.1 Symplectic Transformation
      13.2.2 Harmonic Oscillator Example
      13.2.3 Linear Stability
      13.2.4 Timestep-Dependent Rotation in Phase Space
      13.2.5 Resonance Condition for Periodic Motion
      13.2.6 Resonance Artifacts
13.3 Multiple-Timestep (MTS) Methods
      13.3.1 Basic Idea
      13.3.2 Extrapolation
      13.3.3 Impulses
      13.3.4 Resonances in Impulse Splitting
      13.3.5 Resonance Artifacts in MTS
      13.3.6 Resonance Consequences
13.4 Langevin Dynamics
      13.4.1 Uses
      13.4.2 Heat Bath
      13.4.3 Effect of 
      13.4.4 Generalized Verlet for Langevin Dynamics
      13.4.5 LN Method
13.5 Brownian Dynamics (BD)
      13.5.1 Brownian Motion
      13.5.2 Brownian Framework
      13.5.3 General Propagation Framework
      13.5.4 Hydrodynamics
      13.5.5 BD Propagation
13.6 Implicit Integration
      13.6.1 Implicit vs. Explicit Euler
      13.6.2 Intrinsic Damping
      13.6.3 Computational Time
      13.6.4 Resonance Artifacts
13.7 Future Outlook
      13.7.1 Integration Ingenuity
      13.7.2 Current Challenges
  
14  Similarity and Diversity 
 14.1 Introduction to Drug Design
      14.1.1 Chemical Libraries
      14.1.2 Early Days
      14.1.3 Rational Drug Design
      14.1.4 Automated Technology
      14.1.5 Chapter Overview
14.2 Database Problems
      14.2.1 Database Analysis
      14.2.2 Similarity and Diversity Sampling
      14.2.3 Bioactivity
14.3 General Problem Definitions
      14.3.1 The Dataset
      14.3.2 The Compound Descriptors
      14.3.3 Biological Activity
      14.3.4 The Target Function
      14.3.5 Scaling Descriptors
      14.3.6 The Similarity and Diversity Problem 
14.4 Data Compression and Cluster Analysis
      14.4.1 PCA compression
      14.4.2 SVD compression
      14.4.3 PCA and SVD
      14.4.4 Projection Application
      14.4.5 Example
14.5 Future Perspectives
  
Appendix A Syllabus (Postscript)  (PDF)  
Appendix B Article Reading List  
Appendix C General Reference List  
Appendix D Homeworks  
Bibliography  
References