Drug Designing: Open Access
Open Access

Specificity of Heparin/Heparan sulfate binding to proteins

International Conference and Exhibition on Computer Aided Drug Design & QSAR

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

Umesh R. Desai

Scientific Tracks Abstracts: Drug Design

Abstract :

Heparin/heparan sulfate?protein interactions modulate a number of physiological processes such as coagulation, immune response, angiogenesis, morphogenesis and pathogen infection. A majority of these interactions involve allosteric regulation of the target protein and are poorly understood. We have developed a genetic algorithm-based combinatorial virtual screening approach to understand the nature of interaction of heparin/heparan sulfate with proteins. A dual-filter strategy employing an ?affinity? filter followed by a ?specificity? filter rapidly sorts the combinatorial library into distinct groups of sequences. Application of this strategy on a library of ~46,000 sequences resulted in identification of only five sequences that recognize heparin cofactor II with ?high-affinity and high-specificity?. Comparative analysis of antithrombin?heparin and thrombin?heparin crystal structures using a variety of structural biology tools reveals major differences between the heparin binding pockets of the two proteins. The strategy presents a general approach for understanding specificity features of heparin/heparan sulfate interactions, which are crucial for the development of novel allosteric heparin/heparan sulfate sequences as agonists or antagonists of proteins.

Biography :

Dr. Desai is a Professor of Medicinal Chemistry in the School of Pharmacy at Virginia Commonwealth University, Richmond, VA. He received his Ph.D from the Indian Institute of Technology, Bombay, India, following which he did postdoctoral work with Professors Linhardt (Iowa) and Klibanov (MIT), and an AHA research fellowship with Professor Olson (UIC). Since 1998, he has been at VCU and works on rational design of small and large mechanism-based anticoagulants. He received an Established Investigator Award from the AHA in 2006, and Faculty Research and Teaching Excellence Awards from VCU in 2003 and 2010, respectively.