Drug Designing: Open Access
Open Access

The substrate-envelope approach: A robust tool to design inhibitors against drug targets that exhibit promiscuous molecular specificity

International Conference and Exhibition on Computer Aided Drug Design & QSAR

October 29-31, 2012 DoubleTree by Hilton Chicago-North Shore, USA

Moses Prabu

Accepted Abstracts: Drug Design

Abstract :

A crucial component within HAART is the inhibition of HIV-1 protease. Emergence of drug resistance however, has thwarted the success of perhaps the most extensive structure-based drug design effort. A combined investigation involving X-ray crystallography, biocalorimetry and molecular modeling confirmed that a consensus structural motif assumed by variable substrate sequences (aka substrate-envelope) is responsible for molecular recognition. In addition, the substrate-envelope also elucidates the structural correlation between drug resistance and substrate co-evolution, a crucial mechanism that allows viral efficacy amidst drug therapy. We therefore hypothesize that incorporation of factors intrinsic to substrate recognition in drug development will facilitate the design of novel potent drugs which will also help circumvent drug resistance. Our ongoing effort on other such enzymes with promiscuous recognition sites, such as human cathepsin D and malarial plasmepsins, will also be discussed.