Generating diverse and biologically relevant ensembles of ligand conformers: Addressing flexible rings using a generalized knowledge-based approach

CINF 28

Brian B. Masek, bmasek@tripos.com1, Roman Dorfman2, Karl M. Smith1, and Robert D. Clark, bclark@tripos.com3. (1) Tripos, Inc, 1699 S. Hanley Rd., St. Louis, MO 63144, (2) Informatics Research Center, Tripos, Inc, 1699 South Hanley Road, St. Louis, MO 63144, (3) Informatics Research Center, Tripos, 1699 S. Hanley Rd., St. Louis, MO 63144
Very rapid conformational sampling is critically important in many areas of computer-aided drug design. We have developed an alternative approach wherein a selected force field is used to minimize randomized conformations of a drug-like training set of molecular structures. Torsional profiles characteristic of each type of bond in the training set are then extracted from these conformations. We have extended this method to encompass the treatment of flexible rings and the inversion of pyramidal Nitrogen. The conformations produced are biochemically relevant, as indicated by their ability to efficiently reproduce ligand conformations found in X-ray crystal structures.
 

Herman Skolnik Award Symposium
8:30 AM-12:00 PM, Monday, August 20, 2007 BCEC -- 252 A, Oral

Division of Chemical Information

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007