Molecular Modeling

Kevin Gilbert (Serena Software) and Dabney Dixon (Georgia State University)



The goals of the workshop in molecular modeling are to: introduce college faculty to the theory and practice of molecular modeling with primary emphasis on empirical force field methods; provide sufficient background to enable the participants to understand current modeling practice and limitations; and to use these methods in the classroom as visual aids, as part of the organic chemistry curriculum in understanding structure and reactivity, and as part of the laboratory experience. Participants are introduced to a variety of software packages (PCMODEL, Rasmol, Kinemage, Spartan, Gaussian, and Sybyl or Macromodel), although the emphasis is on the power of the techniques rather than learning how to use the software (which is trivial). Each day of the workshop is divided into lecture and discussion in the morning, and laboratory work in the afternoon.

Day 1: Lecture- Introduction to Molecular Modeling.

A presentation of a comparison of empirical and quantum mechanical methods and an outline of formalisms of empirical force fields, presentation of current force fields (MMX, MM3, MMFF94, Amber, Charm, Opls-AA), and evaluation of parameters. Laboratory: Introduction to PCMODEL. Structure building, minimization with discussion of energy terms and output; exercises building hydrocarbons, alcohols, amines, halides, acids etc.; computing heats of formation, dipole moments, surface areas and volumes; conjugated molecules.

Day 2: Lecture - Conformational Analysis and Minimization.

Participants are introduced to energy minimization methods, searching conformational space, grid searches and stochastic searches. Laboratory: Rotational Energy Profiles. Grid searches; Ramachandran plots; stochastic searches; computation of NMR coupling constants vs experiment; interface to quantum chemistry programs (Gaussian, Gamess, Ampac and Mopac).

Day 3: Lecture - Annealing, Dynamics and Docking.

An introduction to Monte Carlo and simulated annealing, molecular dynamics and docking. Laboratory: Simulated annealing, Monte Carlo and molecular dynamics methods.

Day 4: Lecture 1 - Quantum Mechanics at Various Level of Approximation.  

   Lecture 2 - Modeling Large Molecules - Proteins, DNA, Lipids and Polymers.  

   Laboratory: Rasmol, Kinemage, PDB files, internet sites.

Day 5: Lecture 1 - Modeling inorganic and transition metal complexes,

   Lecture 2 - Introduction to Chemical Informatics.

   Laboratory: Special topics of group choice.