Modeling Biomolecular Systems I

Biology 5476 / Biomedical Engineering 530

Fall Term 2008

Coursemaster: Jay Ponder

Lecturers: Jay Ponder, Nathan Baker, David Sept, Garland Marshall

Teaching Assistant: Tim Williamson

General Information

Syllabus & Schedule [TEXT] [PDF]

Take-Home Final Examination

Exam Questions [PDF]

Monte Carlo vs Molecular Dynamics for Conformational Sampling,
W. L. Jorgensen and J. Tirado-Rives,
Journal of Physical Chemistry, 100, 14508-14513 (1996) [PDF]

Sampling Efficiency of Molecular Dynamics and Monte Carlo Method
in Protein Simulation, H. Yamashita, S. Endo, H. Wako and A. Kidera,
Chemical Physics Letters, 342, 382-386 (2001) [PDF]

Monte Carlo vs Molecular Dynamics for All-Atom Polypeptide Folding
Simulations, J. P. Ulmschnieder, M. B. Ulmschnieder and A. De Nola,
Journal of Physical Chemistry B, 110, 16733-16742 (2006) [PDF]

A Continuum Method for Determining Membrane Protein Insertion Energies
and the Problem of Charged Residues, S. Choe, K. A. Hecht and M. Grabe,
Journal of General Physiology, 131, 563-567 (2008) [PDF]

On the Thermodynamic Stability of a Charged Arginine Side Chain
in a Transmembrane Helix, S. Dorairaj and T. W. Allen,
Proceedings of the National Academy of Sciences USA,
104, 4943-4948 (2007) [PDF]

Assessing the Role of Polarization in Docking, C. J. R. Illingworth,
G. M. Morris, K. E. B. Parkes, C. R. Snell and C. A. Reynolds,
Journal of Physical Chemistry A, 112, 12157-12163 (2008) [PDF]

The Unfoldomics Decade: An Update on Intrinsically Disordered Proteins
K. Dunker, C. J. Oldfield, J. Meng, P. Romero, J. Y. Yang,
J. W. Chen, V. Vacic, Z. Obradovic and V. N. Uversky,
BMC Genomics, 9, S1-S26 (2008) [PDF]

Crystal Structure of a Ten-Amino Acid Protein, S. Honda,
T. Akiba, Y. S. Kato, Y. Sawada, M Sekijima, M. Ishimura,
A. Ooishi, H. Watanabe, T. Odahara and K. Harata,
Journal of the American Chemical Society, 130, 15327-15331 (2008) [PDF]

Extra Precision Glide: Docking and Scoring Incorporating
a Model of Hydrophobic Enclosure for Protein-Ligand Complexes,
R. A. Friesner, R. B. Murphy, M. P. Repasky, L. L. Frye,
J. R. Greenwood, T. A. Halgren, P. C. Sanschagrin and D. T. Mainz
Journal of Medicinal Chemistry, 49, 6177-6196 (2006) [PDF]

ROSETTALIGAND: Protein-Small Molecule Docking
with Full Side-Chain Flexibility, J. Meiler and D. Baker,
PROTEINS, 65, 538-548 (2006) [PDF]

Lecture Summaries

Lecture 1 (Aug 28): Molecular Mechanics Energy Functions [PDF]

Lecture 2 (Sep 2): Electrostatics and Polarization [PDF]

Lecture 3 (Sep 4): Potential Energy Surfaces and Optimization Methods [PDF]

Lecture 4 (Sep 9): Monte Carlo Techniques [PDF]

Lecture 5 (Sep 11): Molecular Dynamics Techniques [PDF]

Lecture 6 (Sep 16): Computation of Properties from Simulation [PDF]

Lecture 7 (Sep 18): User's Guide to Quantum Mechanical Methods [PDF]

Lecture 8 (Sep 23): Structure Determination via Distance Geometry [PDF]

Lecture 9 (Sep 25): Theory & Applications of Free Energy Computations [PDF]

Lecture 10-14 (Sep 30-Oct 14): Computational Electrostatics for Biomolecular Systems
[PDF] [Handout-PDF] [Talk-Quicktime]

Lecture 15-16 (Oct 16-Oct 21): Brownian Dynamics and Kinetics I & II [PDF]

Lecture 17 (Oct 23): Introduction to Free Energy Methods [PDF]

Lecture 18 (Oct 28): Small Molecule and Protein Docking [PDF]

Lecture 19 (Nov 4): Molecular Recognition: The Devil's in the Details [PDF]

Lecture 20 (Nov 6): Systematic Search and Pharmacophores [PDF]

Lecture 21 (Nov 11): Protein Structure Prediction I [PDF]

Lecture 22 (Nov 13): Protein Structure Prediction II [PDF]

Lecture 23 (Nov 18): Heuristic Approaches [PDF]

Lecture 24 (Nov 20): Docking and Virtual Screening [PDF]

Lecture 25 (Nov 25): Designing Enzyme Mimetics [PDF]

Lecture 26 (Dec 2): Experimental Design [PDF]

Lecture 27 (Dec 4): Protein Engineering - An Introduction [PDF]

Handouts & Reading

Force Fields and Simulation

Protein Force Fields, J. W. Ponder and D. A. Case,
Advances in Protein Chemistry, 66, 27-85 (2003) [PDF]

Biomolecular Modeling: Goals, Problems, Perspectives,
W. F. van Gunsteren, D. Bakowies, R. Baron, I. Chandrasekhar, M. Christen,
X. Daura, P. Gee, D. P. Geerke, A. Glattli, P. H. Hunenberger, M. A. Kastenholz,
C. Oostenbrink, M. Schenk, D. Trzesniak, N. F. A. van der Vegt and H. B. Yu,
Angewandte Chemie International Edition, 45, 4064-4092 (2006) [PDF]

Monte Carlo

Monte Carlo and the MANIAC, H. L. Anderson,
Journal of Statistical Physics, 43, 731-748 (1986) [PDF]

Perspective on Monte Carlo Methods, W. L. Jorgensen,
Theoretical Chemistry Accounts, 103, 225-227 (2000) [PDF]

Replica Exchange

Peptide Folding Simulations, S. Gnanakaran, H. Nymeyer,
J. Portman, K. Y. Sanbonmatsu and A. E. Garcia,
Current Opinion in Structural Biology, 13, 168-174 (2003) [PDF]

Atomic Simulations of Protein Folding, Using the Replica Exchange Algorithm,
H. Nymeyer, S. Gnanakaran and A. E. Garcia,
Methods in Enzymology, 383, 119-149 (2004) [PDF]

A Second Look at Canonical Sampling of Biomolecules
Using Replica Exchange Simulation,
D. M. Zuckerman and E. Lyman,
Journal of Chemical Theory and Computation, 2, 1200-1202 (2006) [PDF]

Protein Folding, Design & Engineering

The Protein Folding "Speed Limit", J. Kubelka, J. Hofrichter and W. A. Eaton,
Current Opinion in Structural Biology, 14, 76-88 (2004) [PDF]

Trypsin-Benzamidine Binding Complex

Monte Carlo Simulations for Proteins: Binding Affinities for
Trypsin-Benzamidine Complexes via Free-Energy Perturbations,
J. W. Essex, D. L. Severance, J. Tirado-Rives and W. L. Jorgensen,
Journal of Physical Chemistry B, 101, 9663-9669 (1997) [PDF]

Receptor Rigidity and Ligand Mobility in Trypsin-Ligand Complexes,
O. Guvench, D. J. Price and C. L. Brooks III,
PROTEINS, 58, 407-417 (2005) [PDF]

Calculation of Protein-Ligand Binding Free
Energy by Using a Polarizable Potential,
D. Jiao, P. A. Golubkov, T. A. Darden and P. Ren,
Proc. of the Natl. Acad. of Sci. USA, 105, 6390-6295 (2008) [PDF]

Stochastic & Brownian Dynamics, and Diffusion

Notes on Stochastic Dynamics, D. Sept [PDF]

Notes on Brownian Dynamics, D. Sept [PDF]

Intrinsically Disordered Proteins

The Unfoldomics Decade: An Update on Intrinsically Disordered Proteins
K. Dunker, C. J. Oldfield, J. Meng, P. Romero, J. Y. Yang,
J. W. Chen, V. Vacic, Z. Obradovic and V. N. Uversky,
BMC Genomics, 9, S1-S26 (2008) [PDF]

Docking and Virtual Screening

A Critical Assessment of Docking Programs and Scoring Functions,
G. L. Warren, C. W. Andrews, A.-M. Capelli, B. Clarke, J. LaLonde,
M. H. Lambert, M. Lindvall, N. Nevins, S. F. Semus, S. Senger,
G. Tedesco, I. D. Wall, J. M. Woolven, C. E. Peishoff and M. S. Head,
Journal of Medicinal Chemistry, 49, 5912-5931 (2006) [PDF]

ROSETTALIGAND: Protein-Small Molecule Docking
with Full Side-Chain Flexibility, J. Meiler and D. Baker,
PROTEINS, 65, 538-548 (2006) [PDF]

Sur▀ex-Dock 2.1: Robust Performance from Ligand Energetic Modeling
Ring Flexibility, and Knowledge-Based Search, A. N. Jain,
Journal of Computer-Aided Molecular Design, 21, 281-306 (2007) [PDF]

VALIDATE: A New Method for the Receptor-Based Prediction
of Binding Affinities of Novel Ligands, R. D. Head, M. L. Smythe,
T. I. Oprea, C. L. Waller, S. M. Green and G. R. Marshall,
Journal of the American Chemical Society, 118, 3959-3969 (1996) [PDF]

Modulating G-Protein Coupled Receptor/G-Protein Signal
Transduction by Small Molecules Suggested by Virtual Screening,
C. M. Taylor, Y. Barda, O. G. Kisselev and G. R. Marshall,
Journal of Medicinal Chemistry, 51, 5297-5303 (2008) [PDF]

Ultrafast Shape Recognition for Similarity Search
in Molecular Databases, P. J. Ballester and W. G. Richards,
Proceedings of the Royal Society A, 463, 1307-1321 (2007) [PDF]


The Equilibrium Unfolding of MerP Characterized
by Multivariate Analysis of 2D NMR Data,
A. Berglund, A.-C. Brorsson, B.-H. Jonsson and I. Sethson,
Journal of Magnetic Resonance, 172, 24-30 (2005) [PDF]

Lab Info and Projects

Laboratory 1 (Sep 5): Minimization and Molecular Dynamics [TXT]

Laboratory 2 (Sep 12): Protein MD with Periodic Boundaries [TXT]

Laboratory 3 (Sep 19): Computing Properties of Liquids [TXT] [MOLECULES]

Laboratory 4 (Sep 26): Trypsin-Benzamidine Complex [TXT] [MOLECULES]

Laboratory 5 (Oct 3): Introduction to APBS [APBS] [PDB2PQR]

Laboratory 6 (Oct 24): Protein Association Kinetics [HTML]

Laboratory 7 (Oct 31): Small Molecule Docking [HTML]

Laboratory 8 (Nov 7): Systematic Search & QSAR [PDF]

Laboratory 9 (Nov 14): Homology Modeling [PDF]

Laboratory 10 (Nov 21): Ligand Optimization & de Novo Design [PDF]

Laboratory 11 (Dec 5): Virtual Screening Challenge [PDF]