David L. Mobley Assistant Professor – Medical & Physical B.S., UC Davis 2000 Ph.D., UC Davis 2004 email: dlmobley@uno.edu phone: (504) 383-3662 office: CSB 342

Research Interests Our research focuses on applying computational and theoretical methods to understand and quantitatively predict fundamental biological processes such as protein-ligand binding, solvation, and solubility. We seek to provide an atomically detailed understanding of these processes at a level of accuracy that can be useful in industrial applications. One major area of interest is the binding of small-molecule ligands to proteins. While current computational methods see widespread use in the pharmaceutical industry in drug discovery applications, accuracy is limited and these approaches fall far short of the goal of using computers to suggest new drug candidates. Methods we recently developed and applied have achieved far greater accuracies at computing and even predicting binding affinities than previous methods, so we are working to begin applying these in more complicated and pharmaceutically relevant binding sites. There are also a number of computational challenges involved with accurately modeling larger protein binding sites, so we are working on algorithmic enhancements to deal with these challenges. Another interest is interactions of small molecules with water and other solvents. Accurate modeling of these interactions is important for applying computational tools to drug discovery and other industrial applications, and there are still new insights to be gained into the fundamental chemical physics of these processes. In recent work we have examined the role of entropy in small molecule solvation, and the asymmetric water structure around solutes that are geometrically identical but of opposite polarity. Solute geometry can also affect water structure in a way that is not well understood yet, and we seek to provide a more detailed understanding of some of these phenomena. One goal is to gain new insight and use it to improve approximate models of water that can be used for applications requiring computational speed.

Selected Publications "Charge asymmetries in hydration of polar solutes," D.L. Mobley, A. Barber II, C Fennel, and K.A. Dill, J. Phys. Chem. B 112: 2405-2414 (2008). "Entropy and conformational change in implicit solvent simulations of small molecules," D. L. Mobley, J. D. Chodera and K. A. Dill, J. Phys. Chem. B, 112: 938-946 (2008). "Predicting small-molecule solvation free energies: A blind challenge test for computational chemistry," A. Nicholls*, D. L. Mobley*, J. P. Guthrie, J. D. Chodera, C. I. Bayly, M. D. Cooper, and V. S. Pande, J. Med. Chem. 51: 769-779 (2008). *contributed equally "Accurate and efficient corrections for missing dispersion interactions in molecular simulations," M. R. Shirts*, D. L. Mobley*, J. D. Chodera and V. S. Pande, J. Phys. Chem. B , 111: 13052-13063 (2007). *contributed equally "Predicting absolute ligand binding free energies to a simple model site," D. L. Mobley*, A. P. Graves*, J. D. Chodera, A. C. McReynolds, B. K. Shoichet and K. A. Dill, J. Mol. Biol., 371(4): 1118-1134 (2007). *contributed equally "Confine and Release Method: Obtaining Correct Binding Free Energies in the Presence of Protein Conformational Change," SD. L. Mobley, J. D. Chodera and K. A. Dill, Journal of Chemical Theory and Computation 3(4):1231-1235 (2007). "Comparison of charge models for fixed-charge force fields: Small-molecule hydration free energies in explicit solvent," D. L. Mobley, E. Dumont, J. D. Chodera, and K. A. Dill J. Phys. Chem., B, 111(9): 2242-2254 (2007).