Schlick T. Molecular Modeling and Simulation: An Interdisciplinary Guide
Подождите немного. Документ загружается.
Appendix C. Supplementary Course Texts 565
15. P. Deuflhard, J. Hermans, B. Leimkuhler, A. E. Mark, S. Reich,. R. D. Skeel,
Editors. Computational Molecular Dynamics: Challenges, Methods, Ideas – Pro-
ceedings of the 2nd International Symposium on Algorithms for Macromolecular
Modelling, Berlin, May 21–24, 1997, Lecture Notes in Computational Science and
Engineering, Vol. 4 (Series Editors M. Griebel, D. E. Keyes, R. M. Nieminen,
D. Roose, and T. Schlick), Springer-Verlag, Berlin, 1999.
[Collection of articles from invited presentations to the May 1997 Berlin
workshop on methods for macromolecular modeling. The book contains
sections on the following topics: conformational dynamics, thermody-
namic modeling, enhanced time-stepping algorithms, quantum-classical
simulations, and parallel force field evaluation.]
16. T. E. Creighton, Editor. Protein Folding. W. H. Freeman, New York, NY, 1992.
[Nice collection on general topics regarding protein structure and folding.]
17. D. Eisenberg and D. Crothers. Physical Chemistry with Applications to the Life
Sciences. The Benjamin/Cummings Publishing Company Inc., Menlo Park, CA,
1979.
[Wonderful physical chemistry textbook, with useful biomolecular
information.]
18. R. Elber, Editor. Recent Developments in Theoretical Studies of Proteins.World
Scientific Publishing Company Inc., Singapore, 1996.
[Six chapters on important topics in protein structure and modeling (e.g.,
reaction path studies, analytical theories of protein folding, ion channels, and
protein structure prediction) by the groups of K. Kuczera, R. Elber, J. Straub,
D. Thirumalai, R.S. Eisenberg, and P.G. Wolynes.]
19. A. Fersht. Structure and Mechanism in Protein Science: A Guide to Enzyme
Catalysis and Protein Folding. W. H. Freeman, New York, NY, 1999.
[Comprehensive perspective on both enzyme catalysis and protein folding
by a pioneer researcher, an updated version of the author’s 1995 text on
Enzyme Structure and Mechanism; the text reviews protein structure, em-
phasizing general principles, as well as mentioning recent advances and
insights from theoretical approaches.]
20. M. J. Field. A Practical Introduction to the Simulation of Molecular Systems, second
edition. Cambridge University Press, Cambridge, UK, 2007.
[Introduction to simulation techniques, including potential energy calcu-
lations, conformational/dynamic/thermodynamic sampling, with program
modules in Python.]
21. D. Frenkel and B. Smit. Understanding Molecular Simulations: From Algorithms
to Applications, second edition. Academic Press, San Diego, CA, 2002.
[Excellent introduction to computer simulation of molecular systems, con-
taining a nice mix of mathematical details and more informal, descriptive
text. The focus is on Monte Carlo and molecular dynamics methodologies,
including simple algorithms and numerical illustrations. Some important
recent methodological advances are also included.]
566 Appendix C. Supplementary Course Texts
22. L. M. Gierasch and J. King, Editors. Protein Folding: Deciphering the Second Half
of the Genetic Code. AAAS, Washington D.C., 1990.
[Interesting and beautifully illustrated collection of articles; best bet: Jane
Richardson’s origami analogues of protein folding motifs!]
23. H. Gould, J. Tobochnik, and W. Christian. An Introduction to Computer Simula-
tion Methods: Applications to Physical Systems, third edition. Addison Wesley, San
Francisco, CA, 2007.
[Good introduction to computer simulations, with a focus on classical me-
chanics in Part 1 and statistical physics in Part 2. The material is made highly
accessible to undergraduates by the inclusion of many simple numerical
examples, useful illustrations, and programming segments.]
24. A. Y. Grosberg and A. R. Khokhlov. Giant Molecules: Here, There, and Everywhere
..., second edition. World Scientific Publishing Company, Mountain View, CA,
2009.
[Lively introduction to polymer physics, with nice illustrations and enticing
color plates, aptly fitting a beautiful subject. In the format of a coffee-table
book, the authors cover important subjects like the wide range of polymeric
subjects, ideal chain models and their properties, Brownian motion, biologi-
cal polymers, and polymer dynamics. An accompanying CD-ROM animates
polymer motion, including reptation and coil collapse.]
25. J. M. Haile. Molecular Dynamics Simulation: Elementary Methods. John Wiley &
Sons, Inc., New York, NY, 1992.
[Elementary text on molecular dynamics.]
26. M. H. Kalos and P. A. Whitlock. Monte Carlo Methods, second edition. Wiley-
VCH, Weinheim, Germany, 2008.
[Good introduction to Monte Carlo techniques.]
27. A. R. Leach. Molecular Modelling. Principles and Applications, second edition.
Prentice Hall, Reading, MA, 2001.
[Broad introduction to many aspects of molecular modeling and com-
putational chemistry techniques, covering basic concepts, quantum and
molecular mechanics models, techniques for energy minimization, molec-
ular dynamics, Monte Carlo sampling, protein structure prediction, free
energies, solvation, and drug design applications.]
28. B. Leimkuhler, C. Chipot, R. Elber, A. Laaksonen, A. Mark, T. Schlick, C. Sch¨utte,
R. Skeel, Editors. New Algorithms for Macromolecular Simulation – Proceedings
of the 4th International Workshop on Algorithms for Macromolecular Modeling,
Leicester, UK August 2004, Lecture Notes in Computational Science and Engineer-
ing, Vol. 49 (Series Editors T. J. Barth, M. Griebel, D. E. Keyes, R. M. Nieminen,
D. Roose, and T. Schlick), Springer-Verlag, Berlin, 2006.
[Collection of articles from presentations at the 2004 international workshop
on macromolecular modeling, covering biomolecular simulation meth-
ods and applications. The contributions are grouped under the following
subjects: macromolecular models: from theories to effective algorithms,
Appendix C. Supplementary Course Texts 567
minimization of complex molecular landscapes, dynamical and stochastic-
dynamical foundations, free energy computation, fast electrostatics and
enhanced solvation models, and quantum-chemical models for macro-
molecular simulation.]
29. B. Leimkuhler and S. Reich. Simulating Hamiltonian Dynamics. Cambridge Mono-
graphs on Applied and Computational Mathematics, Cambridge University Press,
Cambridge, UK, 2004.
[Clear exposition of numerical techniques for simulating the dynamics
of conservative systems from a mathematical perspective, including var-
ious integration methods, with simple molecular applications and good
exercises.]
30. K. B. Lipkowitz and D. B. Boyd, Editors Reviews in Computational Chemistry. John
Wiley & Sons, Inc., New York, NY, 1990 – present.
[Nice series of books, with volumes appearing annually with comprehensive
reviews and tutorials on many aspects of computational chemistry.]
31. D. Marx and J. Hutter. Ab Initio Molecular Dynamics: Basic Theory and Advanced
Methods. Cambridge University Press, Cambridge, UK, 2009.
[Introduction to various ab initio molecular dynamics techniques, including
pseudo-code segments and program design.]
32. J. A. McCammon and S. C. Harvey. Dynamics of Proteins and Nucleic Acids.
Cambridge University Press, Cambridge, UK, 1987.
[First book on biomolecular dynamics simulations. Excellent overview of
field.]
33. D. A. McQuarrie. Statistical Mechanics, second edition. University Science Books,
Sausalito, CA, 2000.
[Good reference text to statistical mechanics.]
34. National Research Council Report. Mathematical Challenges from Theoretical /
Computational Chemistry. National Academies Press, Washington D.C., 1995.
(www.nap.edu/readingroom/books/mctcc/).
[Panel report on the opportunities for collaboration, past achievements, and
future possibilities between mathematical and chemical scientists.]
35. P. A. Pevzner. Computational Molecular Biology: An Algorithmic Approach. MIT
Press, Cambridge, MA, 2000.
[Modern text in computational molecular biology mainly addressed to com-
puter scientists and mathematicians interested in discrete algorithms but
accessible to biologists with mathematical grounding. Topics covered in-
clude gene hunting, sequencing and mapping, DNA microarray analysis,
sequence comparison and alignment, genome evolution, and proteomics.]
36. P. von Ragu ´e Schleyer, Editor-in-Chief, and N. L. Allinger, T. Clark, J. Gasteiger,
P. A. Kollman, H. F. Schaefer, III, and P. R. Schreiner, Editors. Encyclopedia of
Computational Chemistry. John Wiley & Sons Inc., West Sussex, UK, 1998.
[Comprehensive reference series (five large volumes) written by experts in
the field.]
568 Appendix C. Supplementary Course Texts
37. D. C. Rapaport. The Art of Molecular Dynamics Simulation, second edition.
Cambridge University Press, Cambridge, UK, 2004.
[Elementary text on molecular dynamics focusing on software details.]
38. W. Saenger. Principles of Nucleic Acid Structure. Springer Advanced Texts in
Chemistry, Springer-Verlag, New York, NY, 1984.
[Wonderful guide to the richness of DNA structure, with an amazing breadth
of topics.]
39. T. Schlick and H. H. Gan, Editors. Computational Methods for Macromolecules:
Challenges and Applications – Proceedings of the 3rd International Workshop on
Algorithms for Macromolecular Modeling, New York, October 12–14, 2000, Lecture
Notes in Computational Science and Engineering, Vol. 24 (Series Editors T. J. Barth,
M. Griebel, D. E. Keyes, R. M. Nieminen, D. Roose, and T. Schlick), Springer-
Verlag, Berlin, 2002.
[Collection of articles from presentations at the 2000 international workshop
on macromolecular modeling, covering biomolecular simulation meth-
ods and applications. The contributions are grouped under the following
subjects: field perspective (preface), biomolecular dynamics applications,
molecular dynamics methods, Monte Carlo methods, other conformational
sampling approaches, free energy methods, long-range interactions and fast
electrostatics, and statistical approaches to protein structures.]
40. R. R. Sinden. DNA Structure and Function. Academic Press, San Diego, CA, 1994.
[Nice modern textbook on DNA structure.]
41. T. Schwede and M. Peitsch, Editors. Computational Structural Biology: Methods
and Applications. World Scientific, Hackensack, NJ, 2008.
[A collection of 27 chapters on structure prediction methods, protein de-
sign, drug discovery, new experimental methods, databases, and molecular
graphics.]
42. G. E. Schulz and R. H. Schirmer. Principles of Protein Structure. Springer
Advanced Texts in Chemistry, Springer-Verlag, New York, NY, 1979.
[Nice advanced text on the rapidly-changing field of protein folding.]
43. J.
ˇ
Sponer and F. Lankaˇs, Editors. Computational Studies of RNA and DNA.Chal-
lenges and Advances in Computational Chemistry and Physics. Springer, Dordrecht,
The Netherlands, 2006.
[A collection of 24 chapters on various aspects of modeling DNA, RNA, and
complexes by various computational approaches.]
44. W. R. Taylor and A. Asz´odi. Protein Geometry, Classification, Topology and Sym-
metry: A Computational Analysis of Structure. Taylor & Francis Group, New York,
NY, 2005.
[Nice introduction to protein structure from a geometric perspective.]
45. W. F. Van Gunsteren and P. K. Weiner, Editors (1989) and W. F. Van Gunsteren,
P. K. Weiner, and A. J. Wilkinson, Editors (1993, 1996): Computer Simulation
Appendix C. Supplementary Course Texts 569
of Biomolecular Systems: Theoretical and Experimental Applications. Vol. 1,2,3.
Springer-Verlag, New York, NY, 1989, 1993, 1996.
[Good series on biomolecular simulations, covering both algorithms and
applications.]
46. G. A. Voth, Editor. Coarse-Graining of Condensed Phase and Biomolecular
Systems. Taylor & Francis Group, Boca Raton, FL, 2009.
[Recent developments in coarse graining modeling of and applications to
complex molecular systems, with examples for peptides and proteins at
various levels of resolution.]
47. D. Wales. Energy Landscapes. Cambridge University Press, Cambridge, UK, 2004.
[Introduction to energy landscape theory, with applications to clusters,
biomolecules and glasses.]
48. A. Warshel. Computer Simulation of Chemical Reactions in Enzymes and Solutions.
John Wiley & Sons, New York, NY, 1991.
[Excellent reference text in the field of computational biological chem-
istry, particularly studies of enzymatic reactions. From basic principles of
chemical bonding and enzyme mechanisms, the authors describe the gov-
erning force fields for molecular simulations, associated algorithms, various
approaches to modeling chemical reactions, and examples of different
mechanisms.]
49. Ahmed H. Zewail, Editor. Physical Biology. From Atoms to Medicine.Imperial
College Press (2008).
[A collection of 20 chapters that provide a beautiful broad overview into the
challenges in our 21st-century biology, including instrumentation and com-
putational advances, protein folding, computer-aided drug discovery, and
sampling approaches for biomolecules.]
Appendix D
Homework Assignments
Please Note: (1) Files mentioned throughout the homeworks can be obtained from
the course site. (2) Insight modeling commands may have changed since the time
of this writing and may need updating by instructor and/or students.
572 Appendix D. Homework Assignments
Assignment 1: Sequence and Structural Databases,
Molecular Modeling Perspective
1. Molecular Modeling Resources. Search the web for resources in molecu-
lar modeling. Look, in particular, for tutorials and instructional material.
A good place to start is the NIH site: cmm.info.nih.gov/modeling/,
which also provides links to many “Related Web Sites”. (Make use of
bookmark-type browser utilities to keep useful web sites handy for future
use).
Submit information from two of the most valuable sites you discover (print-
out) along with a description of how you found the material and what you
found most useful.
2. Sequence and Structure Information Databases. Search the web for pro-
tein (amino-acid) sequence and structure databases. Examples of sequence
databases are: PIR, Swiss-Prot, GenPept, and NRPR.
1
(a) Plot the amount of available sequence database as a function of year,
going back as far as possible, to the 1970s. Plot the information on both a
regular scale and on a logarithm scale.
(b) Similarly, plot the amount of structural
information available as a
function of year, on both a regular and a logarithm scale.
(c) Plot the sequence and structure
information on the same plot in both
standard and logarithm views. What can you say about the rate of growth
1
PIR was established in 1984 by the National Biomedical Research Foundation (NBRF) and
is a good starting point for protein database searching. PIR is somewhat more comprehensive than
SwissProt but smaller and better annotated than GenPept (which also includes many hypotheti-
cal sequences of unknown function. Since 1999, the NBRF has added a new section to PIR called
PAT CH X which contains a non-redundant set of all other protein sequences not included in PIR (from
other databases), with subsequences removed. Thus, PIR supplemented by PAT CH X provides a com-
prehensive collection of protein sequence data in the public domain. Any search through PIR will
automatically include PAT CHX.TheSwissProt database is useful for searches limited to well an-
notated sequences, and GenPept is useful for searching all possible sequences, including those that
have unknown functions.
The best known structural databases are the Protein Data Bank (PDB) and the Nucleic Acid
Database (NDB).
The PDB, managed from 1971 through June 1999 by the Brookhaven National Laboratory, is now
operated by the Research Collaboratory for Structural Bioinformatics (RCSB) (home.rcsb.org/), a
consortium among Rutgers University, the University of California at San Diego, and the National
Institute of Standards and Technology. The RCSB has introduced new features, such as a web-based
tool for data deposition, fast data processing systems, and new search engines (text-based and data-
based), both with extensive reporting capabilities.
The NDB, pioneered in 1992 by the Rutgers RCSB leader Helen Berman, similarly assembles and
distributes structural information about nucleic acids (ndbserver.rutgers.edu/). NDB contains an
atlas, an archive, and a sophisticated search engine to access the data.
Appendix D. Homework Assignments 573
of sequence and structural information? Discuss these finding in relation to
the Human Genome Project.
3. Early Molecular Modeling Literature and Current Progress. Read two
articles dealing with early molecular modeling work:
• B. J. Alder and T. E. Wainwright, “Studies in Molecular Dynamics. I.
General Method”, J. Chem. Phys. 31, 459–466 (1959).
• G. N´emethy and H. A. Scheraga, “Theoretical Determination of Ster-
ically Allowed Conformations of a Polypeptide Chain by a Computer
Method”, Biopolymers 3, 155–184 (1965).
• A. Rahman and F. H. Stillinger, “Molecular Dynamics Study of
Liquid Water”, J. Chem. Phys. 55, 3336–3359 (1971).
Do not worry about not understanding the technical details for now.
Then also read later articles describing current progress in the field and
another discussing issues in validating simulation results:
• J. A. Board, Jr., L. V. Kal´e, K. Schulten, R. D. Skeel, and T. Schlick,
“Modeling Biomolecules: Larger Scales, Longer Durations”, IEEE
Comp.Sci.Eng.1, 19–30 (1994).
• W. F. van Gunsteren and A. E. Mark, “Validation of Molecular
Dynamics Simulation”, J. Chem. Phys. 108, 6109–6116 (1998).
• F. S. Collins, E. D. Green, A. E. Guttmacher, and M. S. Guyer, “A Vi-
sion for the Future of Genomics Research”, Nature 422, 835–847
(2003).
• J. Norberg and L. Nilsson, “Advances in Biomolecular Simulations:
Methodology and Applications”, Quart. Rev. Biophys. 36, 257–306
(2003).
• J. E. Cohen, “Mathematics is Biology’s Next Microscope, Only
Better; Biology is Mathematics’ Next Physics, Only Better”, PLoS
Biology 2 (e439), 2017–2023 (2004).
• T. Schlick, “The Critical Collaboration Between Art and Science: Ap-
plying AnExperimentonaBirdinanAirPumpto the Ramifications
of Genomics on Society”, Leonardo 38 (4), 323–329 (2005).
• W. F. van Gunsteren et al., “Biomolecular Modeling: Goals, Problems,
Perspectives”, Angew.Chem.Int.Ed.45, 4064–4092 (2006).
• M. A. Gerstein et al., “What is a Gene, post ENCODE? History and
Updated Definition”, Genome Research 17, 669–681 (2007).
First describe (in about two pages) the difficulties that Alder and
Wainwright enumerate in 1959 regarding molecular dynamics simula-
tions. Then discuss the issues that are still serious limiting factors today.
Have any of the original limitations been resolved or are likely to be re-
solved in the near future?
574 Appendix D. Homework Assignments
Assignment 2: Introduction to the Insight II Modeling
Package and the PDB File Structure and Retrieval
At this writing, Insight II is available as part of the Discovery Studio
from Accelrys (accelrys.com/products/insight/). Other molecular
modeling packages can be used instead as available.
1. Introduction to Insight II. If you are not familiar with Insight II you might
start by reading the short manual and the tutorial from the web site.
The manual also contains a short list of basic UNIX commands and a de-
scription of simple text editors. Some of the displays on our computers are
slightly different from those described in the tutorial but the differences
are not critical. For example, in our version the help window automatically
follows the tasks invoked from the pulldown menus, and the dial boxes
are located on the left, rather than the right, side of the screen. For more
information, refer to the Insight II User Guide.
Note: after opening Insight II, ignore the message about detection of the
unlicensed mode. Our site does not have license for the Sketch module.
Repeated warning messages might occur during the “build in” Insight II
Pilot tutorial.
2. Running Insight II. Before starting Insight II, you must define the set of
environmental variables by running two commands:
source /local/msi/cshrc
Alternately, you can insert these lines into your .cshrc file and they will
be executed by the system automatically every time you log on. In that case,
you will only need to specify the command
source .cshrc
after editing your .cshrc file the first time. When this insertion is com-
plete, you can run Insight II by specifying the command
insightII
at the UNIX prompt. Remember, UNIX commands are case sensitive.
Note: NYU staff may have already inserted these commands in your
.cshrc file.
3. PDB Structures. Check the PDB web site for information about the type
of stored 3D structures (i.e., proteins, DNA, RNA, DNA/protein complexes,
etc.) and the amount in each group. Report your findings.
4. Retrieval of PDB Files.UsingthewebPDB browser, find coordinate
files for the crystal forms II and III of Bovine Pancreatic Trypsin Inhibitor
(BPTI) among the many BPTI entries. From the PDB Home page, go to
Searching and Browsing PDB and then choose PDB’s web Browser.
You can search by specifying the abbreviation “BPTI” in the Compound
window. When the search is completed, records containing BPTI (includ-
ing its mutated forms) will be displayed at the bottom of the page. Note
Appendix D. Homework Assignments 575
their ID codes (a number followed by three letters). The two middle letters
in this code constitute the name of the subdirectory where the file of in-
terest resides. For example, the subdirectory name for ID code
1abb is
ab and the file name pdb1abb.ent . Ftp to ftp.rcsb.org andloginas
anonymous (the password instructions will be on the screen). Change di-
rectory to
pub/pdb/data/structures/divided/pdb/ab and get the
desired file with the command
get pdb1abb.ent.Z
5. Format of PDB Files. Read the text in the top of both PDB files and
describe the differences in the number of recorded residues, structure reso-
lution, number of solvent molecules, experimental conditions, etc.
Attach to the assignment sheet a printout of a few lines, starting with the
word ATOM, from a PDB file; mark with arrows and describe the con-
tent of each specific format field. (The PDB browser contains information
about the format; see also the original paper on PDB files: J. Mol. Biol.
112, 535–542, 1977).
6. Displaying a Protein in Insight II. Retrieve from PDB the file of mutated
form of BPTI (ID =
7pti), and start Insight II.Fromthetopmenubar
select
Molecule
2
and then choose Get.PressthePDB button in Get File
Typ e and the User button specify the directory. Select the file of the
7pti
structure. (Do not press Heteroatom button). Execute. The structure of
BPTI should now be on the screen. Use
Object / DepthCue and then
Transform / Clip for viewing the protein.
Change the display (
Molecule / Display)toBackbone only to speed up
the response time. Label the mutated residues (
Molecule / Label).
Repeat the operations described above to display the structure of BPTI’s
crystal form II (keep both structures on the screen).
Now, overlay both structures by selecting Overlay
from Transform .In
few paragraphs describe the structural differences between both forms of
BPTI.
7. Ramachandran Plots. To create a file listing with all the dihedral angles φ
and ψ for a protein, you can use
Protein / List from the Biopolymer
module. Select Dihedrals and the protein (any of the structures). Press
List
to file button, specify the file name, and execute. From the recorded
data create a scatter plot (phase diagram), so that each point corresponds to
one (φ, ψ)value.
2
The following notation will be used throughout the homework assignments:
•
Pulldown corresponds to a menu bar pulldown.
• Command
corresponds to a command from the pulldown menu.
• Option corresponds to an option in the dialog box of a given command.