Polar sampling and optimization of protein-ligand cocrystal structures

DESCRIPTION provided by applicant Gfree Bio proposes to collaborate with Professor Bajaj and his group at the University of Texas to develop a general and much more theoretically rigorous algorithm for fitting the ligand binding region of experimental protein ligand cocrystal structures Current methods and practices often lead to very poor geometries for the bound ligand This is a significant impediment to the most effective use of crystallography in drug discovery We will solve this problem by developing an automated method for using polar sampling and optimization in conjunction with the experimental electron density information to correct protein ligand cocrystal structures This methodology will capitalize on recent advances in the Bajaj lab with respect to fast multidimensional optimization linear scaling electrostatics and solvation methods and advanced data structures for representing molecular systems This software has great commercial potential since the problem of properly fitting bound ligands has been receiving increasing attention in the literature and industry As such our solution will have
broad impact on structure based drug design

PUBLIC HEALTH RELEVANCE Gfree Bio will collaborate with Professor Bajajandapos s group at the University of Texas at Austin to develop a new method to solve the problem of ill defined ligand geometries in protein ligand cocrystal structures This program will provide significantly better starting points for structure based design of new drug candidates and contribute to academic and commercial efforts to develop new treatments for a range of diseases