Designing specific or promiscuous drug molecules: Theory, methods development, and application to the HIV-1 system

COMP 191

Mala L Radhakrishnan, mradhakr@wellesley.edu, Department of Chemistry, Wellesley College, 106 Central Street, Wellesley, MA 02481
A designed drug molecule should not only recognize its intended target, but it should also avoid off-target binding and perhaps recognize potential mutant variants of its target to prevent drug resistance. The particular system of which the drug will be a part therefore dictates whether a highly specific or a somewhat promiscuous drug molecule is required. This work combines theoretical analysis, methods development, and application to further the computational treatment of considering multiple target molecules in the drug design process. First, we describe and computationally validate a theoretical framework to understand and predict how structural properties of a biological molecule (size, charge distribution, flexibility, etc.) affect binding promiscuity. Secondly, methods are developed that either select or combinatorially design members of optimally small drug cocktails to collectively recognize multiple target variants. Finally, these methods are applied to design drug cocktails that are predicted to collectively recognize multiple drug-resistant HIV-1 protease mutants.
 

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009