Conformational sampling in a protein-ligand complex environment


Zsolt Zsoldos, Research and Development, Research and Development, SimBioSys Inc, 135 Queen's Plate Dr, Suite 520, Toronto, ON M9W 6V1, Canada
Adequate conformational sampling of small molecule ligands is of high importance in flexible ligand docking as well as in de novo ligand design applications. There are software tools available to generate low energy conformers of ligands, i.e. distinct local minima of the conformational strain energy function of the ligand. Docking and de novo design software often use such sets of conformers or generate them on the fly by use of dihedral angles normally associated with low energy conformers. Conformational statistics of over 5000 high resolution (less than 2.5A) crystal structure complexes from the PDB will be presented. The experimental data demonstrates much wider conformational variation in a protein-ligand complex environment. Requirements are derived from the data for the necessary conformational sampling space and resolution to reproduce the experimental data within acceptable bounds for steric violations. The efficiency of various algorithms to provide the adequate conformational sampling will be compared.

Herman Skolnik Award Symposium
2:00 PM-4:20 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- 110A&B, Oral

Division of Chemical Information

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004