Graduate Faculty Directory
Randy J. Zauhar
Department of Chemistry & Biochemistry
Education
- BS, BA (Eastern Washington)
- MS, PhD (Penn State University)
Title(s)
Director, Graduate Program in Bioinformatics
Faculty Appointments
Associate Professor of Chemistry and Biochemistry
Associate Professor of Bioinformatics
Research Interest
Computational chemistry
Bioinformatics Design of inhibitors against HIV protease and other polymorphic targets
Development of computational methods to determine solvation effects in biological molecules
Computer-aided drug design
Synopsis
Shape signatures is a novel technique for computer-aided drug design developed over the last few years by USP associate professor of biochemistry Randy Zauhar and collaborators. It is a system for compactly representing the shape of drug molecules and the protein receptor sites they target. It was recognized by Emil Fischer in the nineteenth century that the molecules central to the processes of life must recognize each other by a mechanism similar to a key fitting into a lock, and we now recognize that his “lock and key hypothesis” is as central to understanding the mechanics of life as Darwin’s ideas are to understanding evolution and development. The centralidea is complementarity, that bioactive molecules (including metabolites, hormones, and drugs) fit into protein receptors that provide a pocket of the right size and shape to accommodate the small molecule, much like a three-dimensional puzzle. This suggests two routes to identifying new drugs—find molecules similar in shape to a known active or complementary in shape to a known receptor. The shape signatures approach works with either of the two routes just mentioned. The method uses a technique much like ray-tracing to explore the shape of a drug molecule or, alternatively, the shape of a protein receptor pocket. Compact descriptors of shape are generated from the ray-trace, and they can be easily and quickly compared, leading to the capability of rapidly scanning very large chemical libraries for candidate drug molecules.
The method is easily extended to search for other quantities in combination with shape, for example, molecular polarity. Shape signatures is being applied in a number of projects aimed at developing new therapeutics, including COX-2 inhibitors, new estrogenic
compounds, and new opioids.
Publications & Presentations
- “Enrichment of Ligands for the Serotonin Receptor Using the Shape Signatures Approach,” K. Nagarajan, R. Zauhar, and W. J. Welsh, J. Chem.Inform. and Mod., 2005, 45, 49.
- “Shape signatures: A new approach to computer-aided ligand- and receptorbased drug design,” R. J. Zauhar, G. Moyna, L. F. Tian, Z. J. Li, and W. J. Welsh, J. Med. Chem., 2003, 46, 5674.
- “Derivation of C-13 chemical shift surfaces for the anomeric carbons of oligosaccharides and glycopeptides using ab initio methodology,” C. W. Swalina, R. J. Zauhar, M. J. DeGrazia, and G. Moyna, J. Biomol. NMR, 2001, 21, 49.
- “Evidence for a strong sulfur-aromatic interaction derived from crystallographic data,” R. J. Zauhar, C. L. Colbert, R. S. Morgan, and W. Welsh, Biopolymers, 2000, 53, 233.
- “A fast and space-efficient boundary element method for computing electrostatic and hydration effects in large molecules,” R. J. Zauhar and A. Varnek, J. Comp. Chem., 1996, 17, 864.
Attachments
Contact Information
Office:
Science and Technology Center
Room # 222
Box # 100
Phone: 215.596.8691
Email: r.zauhar@usp.edu
