Computational Chemical and Structural Biology
Allosteric Modulators of Neuropeptide Y Receptors
The goal of my project is to identify novel therapeutics for the treatment of obesity using high-throughput screening and quantitative structure activity relationship (QSAR) techniques. With Jan Stichel at Annette Beck-Sickinger’s lab, Leipzig University, Germany and David Weaver, head of the high-throughput screening facilities at Vanderbilt University, I will be screening Vanderbilt’s library of small molecules for potential allosteric modulators of the human Y4 receptor. The primary ligand of Y4 is Pancreatic Polypeptide and is implicated in the negative regulation of appetite. Increasing the activity of pancreatic polypeptide at the Y4 receptor has been suggested as a promising therapeutic for the treatment of obesity.
The second major portion of my project involves a molecular modeling technique known as QSAR. Once the Vanderbilt small molecule library has been screened for potential modulators of the Y4 receptor, I will use the results to design efficient and accurate descriptors that can be used with artificial neural networks to predict activity at the Y4 receptor based on a small molecule’s structural properties. This technique will be used to screen a virtual library of over one million small molecules for leads that can be synthesized and further tested in the cell laboratory.