COMPUTATIONAL STUDY OF LIGAND PROTEIN INTERACTION: HIV STRUCT BASED DRUG DESIGN

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Our research is in structure-based drug design including flexible ligand docking and estimation of ligand binding affinities. Ranking ligand binding affinity is still an unsolved issue in the field of computer-aided drug design. Although we know energy components contributed to binding free energy, we don't know yet how to balance these components to obtain a reliable estimation of the binding free energy. We extensively use the software developed in the Computer Graphics Laboratory to visualize the ligand binding structure, to understand where we made mistakes in our approaches and further more, to improve our energy functions to predict ligand-protein binding free energies. So far we have developed a flexible docking protocol to predict best binding modes for large flexible ligand with more than 16 rotatable bonds. We have proposed a interaction free energy based method to estimate binding free energies. Several pilot calculations show encouraging results.