Session Speaker

Inverse Design of Lead Compounds for Therapeutic Targets
Edwin R. Addison


A new computational chemistry tool for generating lead molecules for drug design, using the inverse design method is presented. Two computational methods, the QM/MM docking mechanism, developed by the Yang group, and the inverse design method, developed jointly by the Beratan and Yang groups at Duke University, will be used to as a first step in developing new drugs, by searching a large part of chemical space for ligands that will be better binders to a specific therapeutic target. Virtual high-throughput, in silico, screening of ligand binding can significantly reduce the time required for lead discovery and lead optimization. One of the most effective tools of in silico binding analysis is the use of docking algorithms to predict rapidly relative binding affinities of a large number of ligands for a given protein. Chemical space is vast, with an estimated 1065 stable molecules accessible with a molecular weight below 850. Designing new drugs that bind to a specified protein target requires finding the best molecule in this vast chemical space. Exploration of this space by direct enumeration and evaluation is prohibitively costly. Rather, one benefits from employing optimization techniques. We suggest here the use of novel "inverse design" method, that can search much more efficiently that large chemical space. Inverse design uses "reverse engineering" methods to solve the problem of going from a set of desired properties back to realistic chemical structures and material morphologies that may have these properties.