"Machines have no judgement and will not remonstrate with us when our will is foolish."

Orson Scott Card, Children of the Mind, 1996

 

 

The primary tools of our research are those of theoretical organic and computational chemistry. Methods ranging from empirical to ab initio in nature are applied to problems in molecular structure and reactivity.

Click here for a nice collection of papers on modern applications in organic chemistry.

 

Quantum Mechanics

Hartree-Fock (HF) methods, post-Hartree-Fock (MPn, coupled cluster, CAS) methods, density functional theory (DFT), exteded Huckel theory, molecular mechanics and combinations thereof are applied to the following problems:

geometry optimization of stable molecules, reactive intermediates, and transition state structures

prediction of activation barriers and energies of reaction

characterization of transition states (using frequency and intrinsic reaction coordinate (IRC) calculations)

conformational analysis of small molecules

geometries and energetics of organometallic systems (using effective core potential, all-electron, and ONIOM methods)

solvent effects (using continuum SCRF and explicit solvation models)

characterization of multicenter bonding

prediction of 1H, 13C, 31P and 15N NMR chemical shifts

prediction of proton affinities, ionization energies, and electron affinities

prediction of kinetic and equilibrium isotope effects

"quantification" of aromaticity (using nucleus-independent chemical shift (NICS) calculations)

quantification of supramolecular stabilization (using theozymes)

prediction of kinetic and equilibrium isotope effects

simulation of dynamic behavior

Software: Gaussian, ADF, GAMESS, Spartan, Macromodel, YAeHMOP

 

 

Docking, Protein Structure Prediction, and Bioinformatics

Automated docking and geometry optimization methods based on molecular mechanics, genetic algorithms and Monte Carlo simulated annealing techniques, as well as bioinformatic methodologies, are applied to the following problems:

prediction of binding modes for small organic molecules to proteins

characterization of binding modes for transition states to enzymes and catalytic antibodies

prediction of the three dimensional structure of proteins (using homology modeling and energy minimization by force fields)

computational mutagenesis

sequence as a predictor of catalytic function and inhibitor or hapten binding

rational drug design

virtual library screening

principal moment of inertia analysis for characterizing combinatorial library diversity

Programs: AutoDock, Insight II, AMBER, GRASP, Procheck, BLAST and ENTREZ at NCBI, GCG programs, Protein Data Bank (PDB)

 

Supercomputing Resources

Supercomputing resources for our research have been generously provided by XSEDE/PSC.