This seminar may be of interest to you:

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Date: Friday, October 21, 2011

Time: 11:00a-12:00p

Location: BH215

Speaker: Prof. Nagarajan Vaidehi

Department of Immunology, Beckman Research Institute, City of Hope Cancer

Research Center

The Role of Conformational Dynamics of G-Protein Coupled

Receptors in Drug Design

Abstract:

The superfamily of membrane proteins known as G-protein coupled receptors

(GPCRs), mediate signal transduction in a wide array of different cell types.

Drugs targeting GPCRs represent the core of modern medicine. Upon stimulation by a variety of signaling molecules (ranging from light to small molecules and large proteins), GPCRs trigger a diverse set of signaling pathways in the cell, by coupling to different intracellular proteins to transduce the signal. This functional diversity in signaling is achieved by the structural conformational dynamics of these receptors. In this talk, I will demonstrate that the combination of computational methods, X-ray crystallography, and fluorescence spectroscopy provides insight into the conformational ensemble sampled by GPCRs.

Additionally, the effect of how the ligand binding leads to a shift in the relative population density in this ensemble will be discussed. An example of how structural insights gained from these fundamental biophysical techniques can be used to design drugs targeting a specific signaling pathway that is relevant in pancreatic cancer will be outlined.