In-silico Drug Design and in-silico screening (Track)




Molecular modelling in drug design: technology and successful examples

Vladimir B. Sulimov
Moscow State University, Research Computer Center, Moscow, Russia

Abstract:

The talk is devoted to the application of molecular modeling to the initial step of the new drugs design – new inhibitors development for a given target protein. Peculiarities of docking and quantum chemistry programs employment for new inhibitors design are discussed. The original docking program SOL based on the genetic algorithm and the respective complex of programs, Keenbase, are described. Keenbase consists of original programs for docking, scoring, atom typification, filtering of undesirable molecular structures, molecular visualization, and auxiliary programs conducting interactive user access to the system resources and computing nodes. Successful example of the new thrombin inhibitors low budget development with usage of the docking facilities as a driving force is presented. Multi-processor functioning of the program SOL performed at supercomputers of Moscow State University is described. Docking of oligopeptides and its possible application for synthetic vaccines development are discussed as well as usage of quantum chemistry calculations for the prediction of ligands conformers energies and protein-ligand chelation energy in the process of the new HIV-integrase inhibitors development. Important role of the desolvation energy and the ligand strain energy terms in the protein-ligand scoring function is discussed. Performance of the original program implementing different implicit solvent models is described.