MUG '01 -- 15th Daylight User Group Meeting -- 6 - 9 Mar 2001

Classification of Biological Binding Sites for Large Scale Design and Virtual Screening of Combinatorial Libraries

Jim Arnold
Prospect Genomics


Prospect Genomics, Inc. is a new company with a mission to develop novel computational technologies to translate genomic information into the discovery and development of drug candidates. The founders of Prospect Genomics include leaders in the fields of protein structure prediction by both comparative modeling and ab-initio methods, protein structure dynamics, the docking of ligands to proteins, and protein structure determination by X-ray crystallography. The company is integrating leading computational technologies, including those of the founders, to create a complete high-throughput software pipeline for in silico screening of organic molecules to multiple biological targets.

This talk will include an introduction of the company as well as presentation of a novel method for integrating information from biological and organic structures.

Two issues that arise in addressing the goal of linking genomic information with the discovery and development of drug candidates are organizing biological structures by their binding characteristics, and using that information to design and screen combinatorial libraries. We have developed two new computer programs that characterize and compare protein structures by the shape, electrostatics, and pocket orientations of their binding sites. We will discuss using these protein pharmacophores to form "gatekeeper" representatives for families of proteins.

The gatekeepers impart a hierarchical organization to protein structures. They have been used to predict the functions of new structures, and we will show how the pharmacophore information is linked to scaffold design.

Daylight Chemical Information Systems, Inc.