Molecular Modeling

The UofL molecular modeling facility, created in 1999 by Dr. John O. Trent, provides support for computational structural biology, molecular visualizations, and in silico drug discovery.  The facility is comprised of six graphics workstations, four Linux servers equipped with a total of 12 state-of-the-art Nvidia GPUs, and a partnership with Dataseam, a ~20,000 processor distributed computing grid for virtual screening.

The Facility is an integral part of experimental therapeutic efforts and works closely with the NMR Facility, the Biophysics facility, molecular biologists, chemists, computer scientists, and biochemists. The core has evolved into a highly collaborative center that provides expertise and resources not available elsewhere in the region. The philosophy of the Facility involves the rationalization of experimental data, the prediction of new empirical experiments, and the structure-based drug design of new agents. These aims are being met by maintaining state-of-the-art software and computational resources that has become the major source of drug discovery at the UofL Health Brown Cancer Center.

The Modeling Facility offers the following primary services:

  • Cryo-EM data analysis and modeling.
  • Modelling of proteins, RNA/DNA, ligands, and lipids (and combinations thereof).
  • Molecular Dynamics (MD) simulations of proteins, nucleic acids, ligands, and lipids (and combinations thereof) to investigate molecular motion, ligand-receptor interactions, or generate molecular model pools.
  • Docking investigations of ligands with their respective or putative receptors.
  • Virtual drug discovery – screen millions of drug-like compounds virtually against a defined protein or nucleic acid receptor using the program Surflex-Dock on the computing grid Dataseam and the UofL CRC.
  • Theoretical biophysical calculations – calculations of various experimentally observable properties of a protein, nucleic acid, or macromolecular assembly (e.g., SASA, sedimentation coefficients, or SAXS scattering curves).
  • Molecular visualizations for manuscript or grant applications.
  • General consultation on any aspect of the above services.

Routine techniques involve ab initio, semi-empirical, empirical (in vacuo, implicit and explicit solvation), QM/MM calculations. Conformational searching: grid searches, simulated annealing, monte carlo, JBW, MC/MD, transition states. Electrostatic surface potentials, partial charges, visualization. DNA, modified DNA, RNA modeling and analysis and drug design including sequence selectivity, Protein Modeling “sequence to drug design” Structure, homology modeling, ala-scanning, stability, dynamics, protein-ligand, protein-protein, and protein-DNA interactions, membrane proteins, electrostatics, hydration, ion association, docking, virtual screening, pharmacophore generation and searching, NMR structures using state of the art advances in Molecular Modeling, Database searching. The Core will work with investigators in all aspects of computational biology.

Contacts:

Robert C. Monsen, Director - or 852-3653
CTR Building Room 222

Jonathan M. Maguire, Manager –