- •Foreword
- •Preface
- •Contents
- •Introduction
- •Oren M. Becker
- •Alexander D. MacKerell, Jr.
- •Masakatsu Watanabe*
- •III. SCOPE OF THE BOOK
- •IV. TOWARD A NEW ERA
- •REFERENCES
- •Atomistic Models and Force Fields
- •Alexander D. MacKerell, Jr.
- •II. POTENTIAL ENERGY FUNCTIONS
- •D. Alternatives to the Potential Energy Function
- •III. EMPIRICAL FORCE FIELDS
- •A. From Potential Energy Functions to Force Fields
- •B. Overview of Available Force Fields
- •C. Free Energy Force Fields
- •D. Applicability of Force Fields
- •IV. DEVELOPMENT OF EMPIRICAL FORCE FIELDS
- •B. Optimization Procedures Used in Empirical Force Fields
- •D. Use of Quantum Mechanical Results as Target Data
- •VI. CONCLUSION
- •REFERENCES
- •Dynamics Methods
- •Oren M. Becker
- •Masakatsu Watanabe*
- •II. TYPES OF MOTIONS
- •IV. NEWTONIAN MOLECULAR DYNAMICS
- •A. Newton’s Equation of Motion
- •C. Molecular Dynamics: Computational Algorithms
- •A. Assigning Initial Values
- •B. Selecting the Integration Time Step
- •C. Stability of Integration
- •VI. ANALYSIS OF DYNAMIC TRAJECTORIES
- •B. Averages and Fluctuations
- •C. Correlation Functions
- •D. Potential of Mean Force
- •VII. OTHER MD SIMULATION APPROACHES
- •A. Stochastic Dynamics
- •B. Brownian Dynamics
- •VIII. ADVANCED SIMULATION TECHNIQUES
- •A. Constrained Dynamics
- •C. Other Approaches and Future Direction
- •REFERENCES
- •Conformational Analysis
- •Oren M. Becker
- •II. CONFORMATION SAMPLING
- •A. High Temperature Molecular Dynamics
- •B. Monte Carlo Simulations
- •C. Genetic Algorithms
- •D. Other Search Methods
- •III. CONFORMATION OPTIMIZATION
- •A. Minimization
- •B. Simulated Annealing
- •IV. CONFORMATIONAL ANALYSIS
- •A. Similarity Measures
- •B. Cluster Analysis
- •C. Principal Component Analysis
- •REFERENCES
- •Thomas A. Darden
- •II. CONTINUUM BOUNDARY CONDITIONS
- •III. FINITE BOUNDARY CONDITIONS
- •IV. PERIODIC BOUNDARY CONDITIONS
- •REFERENCES
- •Internal Coordinate Simulation Method
- •Alexey K. Mazur
- •II. INTERNAL AND CARTESIAN COORDINATES
- •III. PRINCIPLES OF MODELING WITH INTERNAL COORDINATES
- •B. Energy Gradients
- •IV. INTERNAL COORDINATE MOLECULAR DYNAMICS
- •A. Main Problems and Historical Perspective
- •B. Dynamics of Molecular Trees
- •C. Simulation of Flexible Rings
- •A. Time Step Limitations
- •B. Standard Geometry Versus Unconstrained Simulations
- •VI. CONCLUDING REMARKS
- •REFERENCES
- •Implicit Solvent Models
- •II. BASIC FORMULATION OF IMPLICIT SOLVENT
- •A. The Potential of Mean Force
- •III. DECOMPOSITION OF THE FREE ENERGY
- •A. Nonpolar Free Energy Contribution
- •B. Electrostatic Free Energy Contribution
- •IV. CLASSICAL CONTINUUM ELECTROSTATICS
- •A. The Poisson Equation for Macroscopic Media
- •B. Electrostatic Forces and Analytic Gradients
- •C. Treatment of Ionic Strength
- •A. Statistical Mechanical Integral Equations
- •VI. SUMMARY
- •REFERENCES
- •Steven Hayward
- •II. NORMAL MODE ANALYSIS IN CARTESIAN COORDINATE SPACE
- •B. Normal Mode Analysis in Dihedral Angle Space
- •C. Approximate Methods
- •IV. NORMAL MODE REFINEMENT
- •C. Validity of the Concept of a Normal Mode Important Subspace
- •A. The Solvent Effect
- •B. Anharmonicity and Normal Mode Analysis
- •VI. CONCLUSIONS
- •ACKNOWLEDGMENT
- •REFERENCES
- •Free Energy Calculations
- •Thomas Simonson
- •II. GENERAL BACKGROUND
- •A. Thermodynamic Cycles for Solvation and Binding
- •B. Thermodynamic Perturbation Theory
- •D. Other Thermodynamic Functions
- •E. Free Energy Component Analysis
- •III. STANDARD BINDING FREE ENERGIES
- •IV. CONFORMATIONAL FREE ENERGIES
- •A. Conformational Restraints or Umbrella Sampling
- •B. Weighted Histogram Analysis Method
- •C. Conformational Constraints
- •A. Dielectric Reaction Field Approaches
- •B. Lattice Summation Methods
- •VI. IMPROVING SAMPLING
- •A. Multisubstate Approaches
- •B. Umbrella Sampling
- •C. Moving Along
- •VII. PERSPECTIVES
- •REFERENCES
- •John E. Straub
- •B. Phenomenological Rate Equations
- •II. TRANSITION STATE THEORY
- •A. Building the TST Rate Constant
- •B. Some Details
- •C. Computing the TST Rate Constant
- •III. CORRECTIONS TO TRANSITION STATE THEORY
- •A. Computing Using the Reactive Flux Method
- •B. How Dynamic Recrossings Lower the Rate Constant
- •IV. FINDING GOOD REACTION COORDINATES
- •A. Variational Methods for Computing Reaction Paths
- •B. Choice of a Differential Cost Function
- •C. Diffusional Paths
- •VI. HOW TO CONSTRUCT A REACTION PATH
- •A. The Use of Constraints and Restraints
- •B. Variationally Optimizing the Cost Function
- •VII. FOCAL METHODS FOR REFINING TRANSITION STATES
- •VIII. HEURISTIC METHODS
- •IX. SUMMARY
- •ACKNOWLEDGMENT
- •REFERENCES
- •Paul D. Lyne
- •Owen A. Walsh
- •II. BACKGROUND
- •III. APPLICATIONS
- •A. Triosephosphate Isomerase
- •B. Bovine Protein Tyrosine Phosphate
- •C. Citrate Synthase
- •IV. CONCLUSIONS
- •ACKNOWLEDGMENT
- •REFERENCES
- •Jeremy C. Smith
- •III. SCATTERING BY CRYSTALS
- •IV. NEUTRON SCATTERING
- •A. Coherent Inelastic Neutron Scattering
- •B. Incoherent Neutron Scattering
- •REFERENCES
- •Michael Nilges
- •II. EXPERIMENTAL DATA
- •A. Deriving Conformational Restraints from NMR Data
- •B. Distance Restraints
- •C. The Hybrid Energy Approach
- •III. MINIMIZATION PROCEDURES
- •A. Metric Matrix Distance Geometry
- •B. Molecular Dynamics Simulated Annealing
- •C. Folding Random Structures by Simulated Annealing
- •IV. AUTOMATED INTERPRETATION OF NOE SPECTRA
- •B. Automated Assignment of Ambiguities in the NOE Data
- •C. Iterative Explicit NOE Assignment
- •D. Symmetrical Oligomers
- •VI. INFLUENCE OF INTERNAL DYNAMICS ON THE
- •EXPERIMENTAL DATA
- •VII. STRUCTURE QUALITY AND ENERGY PARAMETERS
- •VIII. RECENT APPLICATIONS
- •REFERENCES
- •II. STEPS IN COMPARATIVE MODELING
- •C. Model Building
- •D. Loop Modeling
- •E. Side Chain Modeling
- •III. AB INITIO PROTEIN STRUCTURE MODELING METHODS
- •IV. ERRORS IN COMPARATIVE MODELS
- •VI. APPLICATIONS OF COMPARATIVE MODELING
- •VII. COMPARATIVE MODELING IN STRUCTURAL GENOMICS
- •VIII. CONCLUSION
- •ACKNOWLEDGMENTS
- •REFERENCES
- •Roland L. Dunbrack, Jr.
- •II. BAYESIAN STATISTICS
- •A. Bayesian Probability Theory
- •B. Bayesian Parameter Estimation
- •C. Frequentist Probability Theory
- •D. Bayesian Methods Are Superior to Frequentist Methods
- •F. Simulation via Markov Chain Monte Carlo Methods
- •III. APPLICATIONS IN MOLECULAR BIOLOGY
- •B. Bayesian Sequence Alignment
- •IV. APPLICATIONS IN STRUCTURAL BIOLOGY
- •A. Secondary Structure and Surface Accessibility
- •ACKNOWLEDGMENTS
- •REFERENCES
- •Computer Aided Drug Design
- •Alexander Tropsha and Weifan Zheng
- •IV. SUMMARY AND CONCLUSIONS
- •REFERENCES
- •Oren M. Becker
- •II. SIMPLE MODELS
- •III. LATTICE MODELS
- •B. Mapping Atomistic Energy Landscapes
- •C. Mapping Atomistic Free Energy Landscapes
- •VI. SUMMARY
- •REFERENCES
- •Toshiko Ichiye
- •II. ELECTRON TRANSFER PROPERTIES
- •B. Potential Energy Parameters
- •IV. REDOX POTENTIALS
- •A. Calculation of the Energy Change of the Redox Site
- •B. Calculation of the Energy Changes of the Protein
- •B. Calculation of Differences in the Energy Change of the Protein
- •VI. ELECTRON TRANSFER RATES
- •A. Theory
- •B. Application
- •REFERENCES
- •Fumio Hirata and Hirofumi Sato
- •Shigeki Kato
- •A. Continuum Model
- •B. Simulations
- •C. Reference Interaction Site Model
- •A. Molecular Polarization in Neat Water*
- •B. Autoionization of Water*
- •C. Solvatochromism*
- •F. Tautomerization in Formamide*
- •IV. SUMMARY AND PROSPECTS
- •ACKNOWLEDGMENTS
- •REFERENCES
- •Nucleic Acid Simulations
- •Alexander D. MacKerell, Jr.
- •Lennart Nilsson
- •D. DNA Phase Transitions
- •III. METHODOLOGICAL CONSIDERATIONS
- •A. Atomistic Models
- •B. Alternative Models
- •IV. PRACTICAL CONSIDERATIONS
- •A. Starting Structures
- •C. Production MD Simulation
- •D. Convergence of MD Simulations
- •WEB SITES OF INTEREST
- •REFERENCES
- •Membrane Simulations
- •Douglas J. Tobias
- •II. MOLECULAR DYNAMICS SIMULATIONS OF MEMBRANES
- •B. Force Fields
- •C. Ensembles
- •D. Time Scales
- •III. LIPID BILAYER STRUCTURE
- •A. Overall Bilayer Structure
- •C. Solvation of the Lipid Polar Groups
- •IV. MOLECULAR DYNAMICS IN MEMBRANES
- •A. Overview of Dynamic Processes in Membranes
- •B. Qualitative Picture on the 100 ps Time Scale
- •C. Incoherent Neutron Scattering Measurements of Lipid Dynamics
- •F. Hydrocarbon Chain Dynamics
- •ACKNOWLEDGMENTS
- •REFERENCES
- •Appendix: Useful Internet Resources
- •B. Molecular Modeling and Simulation Packages
- •Index
Appendix: Useful Internet Resources
It is well known that the resources available on the Internet are in constant flux, with new sites appearing on a daily basis and established sites disappearing almost as frequently. This also holds true for the dedicated tools used in biochemical and biophysical studies. New tools are constantly becoming available, and established tools, obsolete. Such rapid change makes it difficult to stay current with the state-of-the-art technologies in the areas of bioinformatics and computational biochemistry and biophysics.
To help the reader keep abreast of these advances we present a list of useful WWW sites in this appendix. Realistically, this list should be updated on a daily basis as many of the tools offered on the Internet are made available not only by large organizations and research groups but also by individual researchers. The goal, therefore, has not been to provide a nearly complete guide to the WWW but rather to provide material representative of the tools useful to researchers in the fields of biochemistry and biophysics.
Most web sites listed contain links to other web sites. This ‘‘hyperconnectivity’’ is what makes the WWW a virtually unlimited information source, which we hope you will be able to exploit to expand the limited list of sites presented below. In addition, this appendix will be regularly updated at the following web site:
http://yuri.harvard.edu/ watanabe or http://www.geocities.com/masakatsu w/index.html
A.Internet Resources for Topics in Selected Chapters
1.Force Fields (Chapter 2)
•MacKerell group: https://rxsecure.umaryland.edu/research/amackere/ research.html
•Popular empirical force field web sites:
CHARMM: http://www.pharmacy.umaryland.edu/ alex/research.html AMBER: http://www.amber.ucsf.edu/amber/
GROMOS: http://igc.ethz.ch/gromos/gromos.html
• Force field evaluation suite: http://www.ccl.net/cca/data/ff evaluation suite/
2.Protein Dynamics (Chapter 3)
•Quick guide to molecular simulations (see Online tutorials, below): http://www.tc.cornell.edu/Visualization/Staff/richard/Courses/biobm631
•Molecular movements database:
http://bioinfo.mbb.yale.edu/MolMovDB/db/ProtMotDB.main.html
3.Minimization and Conformational Analysis (Chapter 4)
•Monte Carlo methods:
http://zarbi.chem.yale.edu/programs/mcpro/mc toc.htm
4.Structure Refinement Applications (Chapter 13)
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•Software for structure determination and analysis: http://www.rcsb.org/pdb/software-list.html
•X-PLOR: A program for structure determination from crystallographic or NMR data: http://atb.csb.yale.edu/xplor
•NMR:
Nilges group: http://www.embl heidelberg.de/nmr/nilges Basics of NMR: http://www.cis.rit.edu/htbooks/nmr/
•X-ray crystallography:
CCP4: http://www.dl.ac.uk/CCP/CCP4/main.html
General site: http://www.iucr.org/cww-top/crystal.index.html
5.Comparative Protein Structure Modeling (Chapter 14)
•Sali’s group: http://guitar.rockefeller.edu/sub-pages/programs.html
6.Statistics in Molecular and Structural Biology (Chapter 15)
Dunbrack group: http://www.fccc.edu/research/labs/dunbrack/
7.Computer-Aided Drug Designs (Chapter 16)
•Tropsha group: http://mmlin1.pha.unc.edu/ jin/QSAR/
•Molecular docking:
http://www.scripps.edu/pub/olson-web/people/gmm/
•Quantitative structure–activity relationship (QSAR): http://www.chem.swin.edu.au/modules/mod4
8.Protein Folding (Chapter 17)
•Becker’s group: http://www.tau.ac.il/ becker/index.html
•Friesner’s group: http://www.chem.columbia.edu/cbs/protein/protein.html
•Okamoto’s group: http://konf2.ims.ac.jp/research.html
9.Membrane Simulations (Chapter 21)
•Tobias’s group: http://www.chem.uci.edu/research/faculty/dtobias.html
•van Gunsteren’s group:
http://www.nmr.chem.ruu.nl/%7Eabonvin/ToT/lukas/index lukas.html
•Feller’s group: http://persweb.wabash.edu/facstaff/fellers/
B. Molecular Modeling and Simulation Packages
Listed is a collection of general-purpose molecular dynamics computer simulation packages for the study of molecular systems. The packages include a wide variety of functionalities for the analysis and simulation of biomolecules. In addition, they contain integrated force fields.
1.CHARMM (Chemistry at HARvard Molecular Mechanics): General-purpose molecular dynamics computer simulation package
http://yuri.harvard.edu/
http://master2.lobos.nih.gov/Charmm/
http://www.scripps.edu/brooks/charmm docs/charmm.html
2.AMBER (Assisted Model Building with Energy Refinement): General-pur- pose molecular dynamics computer simulation package
http://www.amber.ucsf.edu/amber/
3.GROMOS: A general-purpose molecular dynamics computer simulation package for the study of biomolecules http://igc.ethz.ch/gromos/welcome.html
4.GROMACS (GROningen MAchine for Chemical Simulations)
http://rugmd0.chem.rug.nl/ gmx/
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5.TINKER: Software tools for molecular modeling http://dasher.wustl.edu/tinker/
6.NAMD: Object-oriented molecular dynamics code designed for high performance simulation of large biomolecular systems
http://www.ks.uiuc.edu/Research/namd/
7.MMTK (Molecular Modeling ToolKit): Open Source Program library for molecular simulation applications http://starship.python.net/crew/hinsen/MMTK/
C.Molecular Visualization Software
Listed is a collection of visualization software packages that are widely used in academic and industrial research groups.
1.RasMol: A free program that displays molecular structure. It is easy to use and produces space-filling, colored, three-dimensional images.
http://www.bernstein-plus-sons.com/software/rasmol/
2.MOLMOL (MOLecule analysis and MOLecule display): A molecular graphics program for displaying, analyzing, and manipulating the three-dimensional structure of biological macromolecules.
http://www.mol.biol.ethz.ch/wuthrich/software/molmol/
3.WebMol: JAVA PDB viewer to display and analyze structural information. http://www.embl-heidelberg.de/cgi/viewer.pl
4.Swiss-Pdb Viewer: An application that provides a user-friendly interface allowing simultaneous analysis of several proteins.
http://www.expasy.ch/spdbv/mainpage.html
5.WebLab ViewerLite (Freeware from Molecular Simulation, Inc.): A fully Microsoft Windows integrated program allowing for 3D molecular visualization and the generation of high quality rendered images.
http://www.msi.com/download/index.html
6.Jmol: A free, open source molecule viewer and editor. http://www.openscience.org/jmol
Jmol can be also used to animate the results of simulations that are in a multiframe XYZ format and to animate the computed normal modes from ab initio quantum chemistry packages.
7.VMD (Visual Molecular Dynamics): MD-generated trajectories can be read. http://www.ks.uiuc.edu/Research/vmd/
VMD is designed for the visualization and analysis of biological systems such as proteins, nucleic acids, and lipid bilayer assemblies. It may be used to view more general molecules, as VMD can read several different structural file formats and display the contained structure. VMD provides a wide variety of methods for rendering and coloring a molecule. VMD can be used to animate and analyze the trajectory of a molecular dynamics (MD) simulation.
8.gOpenMol: Graphical interface of computational chemistry http://www.csc.fi/ laaksone/gopenmol/gopenmol.html
gOpenMol can be used for the analysis and display of molecular dynamics trajectories and the display of molecular orbitals, electron densities, and electrostatic potentials from programs like the Gaussian.
9.Molscript: A program for displaying molecular 3D structures in both schematic and detailed representations. http://www.avatar.se/molscript/.
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10.List of other free or public domain software that is relevant to visualizations: http://www.ahpcc.unm.edu/ aroberts/main/free.htm
D.Computational Biophysics Related at the National Institutes of Health (NIH)
1.General home page: http://webasaurus.dcrt.nih.gov//molbio/
2.Scientific resources: http://helix.nih.gov/science/
3.Sequence and molecular databases: http://helix.nih.gov/science/databases.html
4.Center for Molecular Modeling: http://cmm.info.nih.gov/modeling/
5.Molecular biology software list: http://bimas.dcrt.nih.gov/sw.html
E.Molecular Biology Software Links
1.Resource site for biotechnology—Molecular biology, bioinformatics, biophys-
ics, and biochemistry—A well-organized web site: http://www.ahpcc.unm.edu/ aroberts/
2.Molecular surface package: http://www.best.com/ connolly/
3.Biotechnological software and internet journal: http://www.davincipress.com/bsj.html
4.Computational chemistry web site: http://www.ccl.net/chemistry/
F.Online Tutorials
1.Molecular dynamics:http://cmm.info.nih.gov/intro simulation/course for html.html http://www.chem.swin.edu.au/modules/mod6.
2.Monte Carlo method:
http://www.cooper.edu/engineering/chemechem/MMC/tutor.html. http://www.cooper.edu/engineering/chemechem/monte.html
3.Bioinformatics:
http://www.iacr.bbsrc.ac.uk/notebook/wwwresource/bioinformaticcourses392.htm http://biotech.icmb.utexas.edu/pages/bioinfo.html.
4.Molecular modeling workbook:
http://www.ch.ic.ac.uk/local/organic/mod/Chem99.pdf
G.Additional Resource List for Computational Chemistry and Molecular Modeling Software
1.The Center for Molecular Modeling at NIH: http://cmm.info.nih.gov/modeling/software.html
2.Laboratory of Structural Biology at NIEHS: http://dir.niehs.nih.gov/dirlmg/strFxn.html
3.BioMolecular research tools—A collection of WWW links to information and
services useful to molecular biologists:
http://www.public.iastate.edu/ pedro/research tools.html
4.Center for Scientific Computing in Finland: http://www.csc.fi/ laaksone/docs/stuff.html
5.Rolf Claessen’s chemistry index:
http://www.claessen.net/chemistry/soft mod en.html
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6.Software for structure determination and analysis at the Protein Data Bank: http://www.rcsb.org/pdb/Modeling
7.W. L. Jorgensen group at Yale: http://zarbi.chem.yale.edu/
H.Databases of Biological Molecules
1.Protein Data Bank: http://www.rcsb.org/pdb/
2.IMB Jena Image Library of Biological Macromolecules: http://www.imb-jena.de/IMAGE.html
3.Nucleic Acid Database: http://ndbserver.rutgers.edu/NDB/
4.Cambridge Structural Database: http://www.ccdc.cam.ac.uk
5.Molecules R Us: http://molbio.info.nih.gov/cgi-bin/pdb
6.ExPASy (Expert Protein Analysis System) molecular biology server: http://www.expasy.ch
7.Lists of useful databases (including the Genome database) http://www.gdb.org/gdb/hgpresources.html