Chemistry 430

Spring Term 2019

Instructor: Jay Ponder


Syllabus & Schedule [PDF]


Take-Home Final Exam [PDF]

References for Exam Question 2 [Files]


Lecture 1 (Jan 14): Overview of Molecular Modeling [PDF]

Lecture 2 (Jan 16): Introduction to Molecular Mechanics I [PDF]

Lecture 3 (Jan 23): Introduction to Molecular Mechanics II

Lecture 4 (Jan 28): Potential Energy Surfaces & Optimization Methods [PDF]

Lecture 5 (Jan 30): Basics of Molecular Dynamics Simulation I [PDF]

Lecture 6 (Feb 04): Basics of Molecular Dynamics Simulation II

Lecture 7 (Feb 06): Computing Properties from Molecular Dynamics [PDF]

Lecture 8 (Feb 11): Introdution to Monte Carlo Methods I [PDF]

Lecture 9 (Feb 13): Introdution to Monte Carlo Methods II

Lecture 10 (Feb 18): Methods for Free Energy Calculations [PDF]

Lecture 11 (Feb 20): Electrostatics & Solvation in Biomolecular Systems I [PDF]

Lecture 12 (Feb 25): Electrostatics & Solvation in Biomolecular Systems II

Lecture 13 (Feb 27): Proteins I: Amino Acids & Secondary Structure [PDF]

Lecture 14 (Mar 04): Proteins II: Tertiary Structure, Motifs & Fold Classes [PDF]

Lecture 15 (Mar 06): Proteins III: Mechanism of Protein Folding [PDF]

Lecture 16 (Mar 18): Basics of ab Initio Molecular Orbital Theory I [PDF]

Lecture 17 (Mar 20): Basics of ab Initio Molecular Orbital Theory II

Lecture 18 (Mar 25): Mathods for Treating Electron Correlation [PDF]

Lecture 19 (Mar 27): Semi-Empirical Molecular Orbital Methods [PDF]

Lecture 20 (Apr 01): Density Functional Theory (DFT) [PDF]

Lecture 21 (Apr 03): Frontier Molecular Orbital (FMO) Theory [PDF]

Lecture 22 (Apr 08): Protein Structure Prediction, Engineering & Design [PDF]

Lecture 23 (Apr 10): Small Molecule & Protein Docking I [PDF]

Lecture 24 (Apr 15): Small Molecule & Protein Docking II

Lecture 25 (Apr 17): Computing Binding Rate Constants via Brownian Dynamics [PDF]

Lecture 26 (Apr 22): Introduction to Convolutional Neural Networks [PDF]

Lecture 27 (Apr 24): Machine Learning in Computational Chemistry [PDF]


Introduction to Using a Linux Terminal Window

Unix for the Beginning Mage, J. Topjian [PDF]

Useful Unix/Linux Tools [HTML]

Perspectives on Molecular Modeling

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]

Biomolecular Modeling and Simulation: A Field Coming of Age,
T. Schlick, R. Collepardo-Guevara, L. A. Halvorsen, S. Jung and X. Xiao,
Quarterly Reviews of Biophysics, 44, 191-228 (2011) [PDF]

Molecular Mechanics & Force Fields

Empirical Force Field Models, Chapter 4 from Molecular Modelling:
Principles & Applications, 2nd Edition by A. R. Leach, [PDF]

Biomolecular Force Fields: Where Have We Been, Where Are We Now,,
Where Do We Need To Go and How Do We Get There?, P. Dauber-Osguthorpe
and A. T. Hagler, Journal of Computer-Aided Molecular Design, XX, 1-71 (2018) [PDF]

Force Field Development Phase II: Relaxation of Physics-Based
Criteria... or Inclusion of More Rigorous Physcs Into the Representation
of Molecular Physics, A. T. Hagler, Journal of Computer-Aided Molecular
Design, XX, 1-60 (2018) [PDF]

Nonlinear Optimization Methods

Energy Minimization & Related Methods, Chapter 5 from Molecular Modelling:
Principles & Applications, 2nd Edition by A. R. Leach, [PDF]

Optimization Methods in Computational Chemistry, T. Schlick,
Reviews in Computational Chemistry, 3, 1-71 (1992) [PDF]

Molecular Dynamics Simulation

Simulation Methods & Molecular Dynamics, Chapter 6 & 7 from Molecular
Modelling: Principles & Applications, 2nd Edition by A. R. Leach, [PDF]

Molecular Dynamics, J. Meller,
Encyclopedia of Life Sciences, 1-8 (2001) [PDF]

Introduction to Molecular Dynamics Simulation, M. P. Allen,
Computational Soft Matter, NIC Series, 23, 1-28 (2004) [PDF]

Molecular Dynamics: Survey of Methods for Simulating
the Activity of Proteins, S. A. Adcock and J. A. McCammon,
Chemical Reviews, 106, 1589-1615 (2006) [PDF]

History of the Monte Carlo Method

Equation of State Calculations by Fast Computing Machines,
N. Metropolis, A. W. Rosenbluth, M. N. Rosenbluth, A. H. Teller and E. Teller,
Journal of Chemical Physics, 21, 1087-1092 (1953) [PDF]

Perspectives on "Equation of State Calculations by Fast Computing
Machines", W. L. Jorgensen, Theoretical Chemistry Accounts,
103, 225-227 (2000) [PDF]

The Beginning of the Monte Carlo Method,
N. Metropolis, Los Alamos Science, 14, 125-130 (1987) [PDF]

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

Monte Carlo Theory and Algorithms

Monte Carlo Simulation Methods, Chapter 8 from Molecular Modelling:
Principles & Applications, 2nd Edition by A. R. Leach, [PDF]

Progress and Outlook in Monte Carlo Simulations, D. N. Theodorou,
Industrial & Engineering Chemistry Research, 49, 3047-3058 (2010) [PDF]

Monte Carlo Simulations, D. J. Earl and M. W. Deem,
Methods in Molecular Biology, 443, 25-36 (2008) [PDF]

Monte Carlo Codes, Tools and Algorithms, D. Dubbledam, A. Torres-Knoop
and K. S. Walton, Molecular Simulation, 39, 1253-1292 (2013) [PDF]

Free Energy Calculations

Free Energy Calculations, Chapter 11 from Molecular Modelling:
Principles & Applications, 2nd Edition by A. R. Leach, [PDF]

Free Energy Calculations in Structure-Based Drug Design, M. R. Shirts,
D. L. Mobley and S. P. Brown, Chapter 5 from Drug Design: Structure- and
Ligand-Based Approaches, by K. M. Merz Jr., D. Ringe and C. H. Reynolds [PDF]

Towards Accurate Free Energy Calculations in Ligand
Protein-Binding Studies, T. Steinbrecher and A. Labahn,
Current Medicinal Chemistry, 17, 767-785 (2010) [PDF]

Efficient Estimation of Free Energy Differences from Monte Carlo Data,
C. H. Bennett, Journal of Computational Physics, 22, 245-268 (1976) [PDF]

Accurate Calculation of the Absolute Free Energy of Binding for Drug
Molecules, M. Aldeghi, A. Heifetz, M. J. Bodkin, S. Knapp and P. C. Biggin,
Chemical Science, 7, 207-218 (2016) [PDF]

Biomolecular Electrostatics and Solvation

Poisson's Equation in Electrostatics, J.-L. Liu, March 2011 [PDF]

Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics,
W. C. Still, A. Tempczyk, R. C. Hawley and T. Hendrickson,
Journal of the American Chemical Society, 112, 6127-6129 (1990) [PDF]

Computational Methods for Biomolecular Electrostatics, F. Dong,
B. Olsen and N. A. Baker, Methods in Cell Biology, 84, 843-870 (2008) [PDF]

Biomolecular Electrostatics and Solvation: A Computational Perspective,
P. Ren, J. Chun, D. G. Thomas, M. J. Schnieders, M. Marcho, J. Zhang
and N. A. Baker, Quarterly Reviews of Biophysics, 45, 427-491 (2012) [PDF]

Classical ElectrostatiMcs for Biomolecular Simulations, G. A. Cisneros,
M. Karttunen, P. Ren and C. Sagui, Chemical Reviews, 114, 779-814 (2014) [PDF]

Comparative & Homology Modeling

Protein Structure Modeling with MODELLER, B. Webb and A. Sali,
Methods in Molecular Biology, 1654, 39-54 (2017) [PDF]

SWISS-MODEL: Homology Modelling of Protein Structures and Complexes,
A. Waterhouse, M. Bertoni, S. Beinert, G. Studer, G. Tauriello, R. Gumienny,
F. T. Heer, T. A. P. de Beer, C. Rempfer, L. Bordoli, R. Lepore and T. Schwede,
Nucleic Acids Research, 46, W296-303 (2018) [PDF]

The Phyre2 Web Portal for Protein Modeling, Prediction and Analysis,
L. A. Kelley, S. Mezulis, C. M. Yates, M. N. Wass and M. J. E. Sternberg,
Nature Protocols, 10, 845-858 (2015) [PDF]

ab Initio Molecular Orbital Theory

Computational Quantum Mechanics & Advanced ab Initio Methods,
Chapters 2 & 3 from Molecular Modeling, 2nd Edition by A. R. Leach [PDF]

Proof of the Variational Theorem, Appendix B from
Introduction to Computational Chemistry, 2nd Edition, by F. Jensen,
John Wiley & Sons, Chichester UK, 2007 [PDF]

Derivation of the Hartree-Fock Equation, Appendix 7 from
Quantum Chemistry, 3rd Edition, by J. P. Lowe and K. A. Peterson,
Elsevier Academic Press, Amsterdam, 2006 [PDF]

The RHF Dissociation Problem, Section 4.3 from Introduction
to Computational Chemistry, 2nd Edition, by F. Jensen,
John Wiley & Sons, Chichester UK, 2007 [PDF]

Approximate Molecular Orbital Methods

The Extended Huckel Method, Chapter 10 from
Quantum Chemistry, 3rd Edition by J. P. Lowe and K. A. Peterson [PDF]

Basic Theory of the FMO Method, Chapters 2 & 3
from Frontier Orbitals, by N. T. Anh [PDF]

An Examination of the Nature of Localized Molecular Orbitals and
their Value in Understanding Phenomena that Occur in Organic Chemistry,
J. J. P. Stewart, Journal of Molecular Modeling, 25, 7 (2019) [PDF]

Density Functional Theory

Obituary: Density Functional Theory (1927-1993), P. M. W. Gill,
Australian Journal of Chemistry, 54, 661-662 (2001) [PDF]

Density Functional Theory (DFT), Hartree-Fock (HF), and
the Self-Consistent Field, P. M. W. Gill,
Encyclopedia of Computational Chemistry, 1, 678-689 (1998) [PDF]

Perspective: Fifty Years of Density-Functional Theory
in Chemical Physics, A. D. Becke,
Journal of Chemical Physics, 140, 18A301 (2014) [PDF]

DFT in a Nutshell, K. Burke and L. O. Wagner,
International Journal of Quantum Chemistry, 113, 96-101 (2013) [PDF]

Can Orbitals Really Be Observed? [Warning! Philosophy...]

Can Orbitals Really Be Observed in Scanning Tunneling
Microscopy Experiments, B. Q. Pham and M. S. Gordon,
Journal of Physical Chemistry A, 121, 4851-4852 (2017) [PDF]

Are Orbitals Observable?, P. Mulder,
International Journal for Philosophy of Chemistry, 17, 24-35 (2011) [PDF]

Measuring Orbitals: Provocation or Reality?, W. H. E. Schwarz,
Angewandte Chemie International Edition, 45, 1508-1517 (2006) [PDF]

Molecular Docking Methods

Challenges and Advances in Computational Docking: 2009 in Review,
E. Yurlev, M. Agostino and P. A. Ramsland,
Journal of Molecular Recognition, 24, 149-164 (2011) [PDF]

Protein-Ligand Docking in the New Millennium - A Retrospective of 10
Years in the Field, S. F. Sousa, A. J. M Ribeiro, J. T. S. Coimbra,
R. P. P. Neves, S. A. Martins, N. S. H. N. Moorthy, P. A. Fernandes and
M. J. Ramos, Current Medicinal Chemistry, 20, 2296-2314 (2013) [PDF]

Molecular Docking and Structure-Based Drug Design Strategies,
L. G. Ferreira, R. N. dos Santos, G. Oliva and A. D. Andricopulo,
Molecules, 20, 13384-13421 (2015) [PDF]

Software for Molecular Docking: A Review, N. S. Pagadala,,
K. Syed and J. Tuszynski, Biophysical Reviews, 9, 91-102 (2017) [PDF]

Structure-based Discovery of Opioid Analgesics with Reduced Side Effects,
A. Manglik, H. Lin, D. K. Aryal, J. D. McCorvy, D. Dengler, G. Corder,
A. Levit, R. C. Kling, V. Bernat, H. Hubner, X.-P. Huang, M. F. Sassano,
P. M. Giguere, S. Lober, D. Duan, G. Scherrer, B. K. Kobilka, P. Gmeiner,
B. L. Roth and B. K. Shoichet, Nature, 537, 185-190 (2016) [PDF]

AutoDock Search and Scoring Methodology

Automated Docking Using a Lamarckian Genetic Algorithm and an
Empirical Binding Free Energy Function, G. M. Morris, D. S. Goodsell,
R. S. Halliday, R. Huey, W. E. Hart, R. K. Belew and A. J. Olsen,
Journal of Computational Chemistry, 19, 1639-1662 (1998) [PDF]

A Semiempirical Free Energy Force Field with Charge-Based Desolvation,
R. Huey, G. M. Morris, A. J. Olsen and D. S. Goodsell,
Journal of Computational Chemistry, 28, 1145-1152 (2007) [PDF]

Brownian Dynamics Simulation

Biological Applications of Electrostatic Calculations
and Brownian Dynamics Simulations, J. D. Madura, M. E. Davis,
M. K. Gilson, R. C. Wade, B. A. Luty and J. A. McCammon,
Reviews in Computational Chemistry, 4, 229-267 (1994) [PDF]

Brownian Dynamics, Molecular Dynamics, and Monte Carlo
Modeling of Colloidal Systems, J. C. Chen and A. S. Kim,
Advances in Colloid and Interface Science, 112, 159-173 (2004) [PDF]

Convolutional Neural Networks

A Quick Introduction to Neural Networks,
U. J. J. Walkarn, The Data Science Blog, August 2016 [PDF]

An Intuitive Explanation of Convolutional Neural Networks,
U. J. J. Walkarn, The Data Science Blog, August 2016 [PDF]

Machine Learning Applications

Transferable Atomic Multipole Machine Learning Models for Small,
Organic Molecules, T. Bereau, D. Andrienko and O. A. von Lileinfeld,
Journal of Chemical Theory and Computation, 11, 3225-3233 (2015) [PDF]


General Information

How to Install Non-AppStore Programs on MacOS [PDF]

How to Disable the (Annoying!) Gatekeeper on MacOS [PDF]

Avogadro & Avogadro2: Molecular Editors

Avogadro 1.2.0 Software for MacOS [DMG]

Avogadro 1.2.0 Software for Windows [EXE]

Avogadro2 1.91 Software for MacOS [DMG]

Avogadro2 1.91 Software for Windows [EXE]

Learning Avogadro [PDF]

Avogadro Example Files [GZIPPED TAR]

Chimera: Extensible Molecular Modeling System

Chimera 1.13 Software for MacOS [DMG]

Chimera 1.13 Software for Windows [EXE]

Chimera 1.13 Software for Linux [BIN]

Chimera Quick Reference [PDF]

Chimera Getting Started [HTTP]

Chimera User's Guide [HTTP]

PyMOL: Python-Enhanced Molecular Graphics

PyMOL Software for MacOS [DMG]

PyMOL Software for Windows [MSI]

PyMOL Software for Linux [GZIPPED TAR]

PyMOL Quick Reference [PDF]

PyMOL Introduction [PDF]

PyMOL Tutorial [PDF]

PyMOL User's Guide [PDF]

VMD: Visual Molecular Dynamics

VMD 1.9.4 Software for MacOS [DMG]

VMD 1.9.3 Software for Windows [MSI]

VMD 1.9.4 Software for Linux [GZIPPED TAR]

VMD User's Guide [PDF]

Using VMD Tutorial [PDF]

VMD Tutorial Files [GZIPPED TAR]

FFE: Force Field Explorer

Force Field Explorer 8.5.3 Software for MacOS [DMG]

Force Field Explorer 8.5.3 Software for Windows [ZIP]

Force Field Explorer 8.5.3 Software for Linux [GZIPPED SH]

Force Field Explorer Manual [PDF]

Tinker: Software Tools for Molecular Design

Tinker 8.5.3 Software for MacOS [GZIPPED TAR]

Tinker 8.5.3 Software for Windows [ZIP]

Tinker 8.5.3 Software for Linux [GZIPPED TAR]

Tinker Manual [PDF]

Spartan Molecular Modeling (Q-Chem)

Spartan Student Overview [PDF]

Spartan Student Tutorial [PDF]

Walking Through Spartan Student (input file for tutorial) [Input]

Spartan '16 Manual [PDF]

Q-Chem 5.1 Manual [PDF]

Gaussian Quantum Chemistry

Gaussian 16 Online Manual [HTML]

GaussView 6 Online Manual [HTML]

APBS: Adaptive Poisson-Boltzmann Solver

APBS 1.3 Software for MacOS [GZIPPED TAR]

APBS 1.3 Software for Windows [ZIP]

APBS 1.3 Software for Linux [GZIPPED TAR]

PDB2PQR Command Line Usage [HTML]

APBS Command Line Usage [HTML]

APBS Input Files & Options [HTML]

pKa Calculations in APBS [HTML]

Tutorial: APBS, PDB2PQR, PyMol and VMD [HTML]

Tutorial: Lysozyme pKa Example for PDB2PQR [HTML]

Modeller: Comparative Protein Structure Modeling

Modeller 9.21 Software for MacOS [DMG]

Modeller 9.21 Software for Windows [ZIP]

Modeller 9.21 Software for Linux (Ubuntu & Debian) [DEB]

Modeller 9.21 Software for Linux (RedHat & CentOS) [RPM]

Modeller 9.21 Installation Instructions [PDF]

Modeller 9.21 Manual [PDF]

Chimera Interface to Modeller [PDF]

Tutorial: Modeling Based on a Single Template [PDF] Files [GZIPPED TAR]

Tutorial: Multiple Templates, Loop Refinement & User Restraints [PDF]

Tutorial: The Alignment-Modeling-Evaluation Cycle [PDF]

Tutorial: Modeling a Sequence after Fold Assignment [PDF]

Tutorial: Use of Cryo-EM Data in Modeling [PDF]

AutoDock & MGLTools: Automated Molecular Docking

AutoDock 4.2.6 Software for MacOS [TAR]

AutoDock 4.2.6 Software for Windows [ZIP]

AutoDock 4.2.6 Software for Linux [TAR]

AutoDock Installation for Linux & MacOS [PDF]

AutoDock Installation for Windows [PDF]

AutoDock User's Guide [PDF]

MGLTools 1.5.7 Software for MacOS [DMG]

MGLTools 1.5.7 Software for Windows [ZIP]

MGLTools 1.5.7 Software for Linux [SCRIPT]

XQuartz 2.7.11 for MacOS (needed by MGLTools on Mac) [DMG]

Tutorial: Docking Indinavir to HIV Protease [PDF]

Tutorial: Docking of BACE1 with an Inhibitor [PDF]

SDA7: Simulation of Diffusional Association

SDA7 Documentation [HTML]


Suggested Lab Report Format [PDF]

Lab 1 (Jan 18): Unix Tutorial; Using Chimera, VMD, FFE & Spartan [Files]

Lab 2 (Jan 25): Conformational Analysis of Alanine Dipeptide [Files]

Lab 3 (Feb 01): Liquid Properties via Molecular Dynamics Simulation [Files]

Lab 4 (Feb 08): Global Optimization of Lennard-Jonesium & Polyalanine [Files]

Lab 5 (Feb 15): Relative Hydration Free Energy of Monovalent Ions [Files]

Lab 6 (Feb 22): APBS Poisson-Boltzmann Calculations on Lysozyme [Files]

Lab 7 (Mar 01): Homology Modeling of a Lactate Dehydrogenase [Files]

Lab 8A (Mar 08): Folding Simulations of the TrpCage MiniProtein [Files]

Lab 8B (Mar 22): Folding Simulations of the TrpCage MiniProtein (Cont.)

Lab 9 (Mar 29): Computing the Rotational Barrier in Hydrazine [Files]

Lab 10 (Apr 05): Frontier Molecular Orbital Analysis of Regioselectivity [Files]

Lab 11 (Apr 12): Docking Indinavir to HIV Protease Using AutoDock [Files]

Lab 12 (Apr 19): Diffusional Association of the Barnase-Barstar Complex [Files]