Grossfield Lab

Dr. Alan Grossfield
Department of Biochemistry and Biophysics, Box 712
University of Rochester Medical Center
Rochester, New York 14642
Phone: 585 276 4193 Fax: 585 275 6007
alan_grossfield [at] urmc.rochester.edu

Lab Research

• Mechanism of Antimicrobial lipopeptides. Antimicrobial lipopeptides are short peptides fused with fatty acids, which have recently been shown to selectively lyse bacterial cells while leaving mammalian cells unharmed. We are using molecular dynamics simulations of two lipopeptide species bound to lipid bilayers with compositions mimicing bacterial and mammalian membranes to explore the poration mechanism. This work is done in collaboration with Mike Pitman at IBM Research and Scott Feller at Wabash College.
• Structure and function of GPCRs. We have collaborated with IBM Research on a series of unprecedentedly long all-atom molecular dynamics simulations of GPCRs, specifically rhodopsin and (more recently) the cannabinoid receptor. This work is done in collaboration with Mike Pitman at IBM Research, Scott Feller at Wabash College, Dow Hurst and Patricia Reggio at the University of North Carolina-Greensboro, and Diane Lynch of Kennesaw State.
• Implicit membrane modeling. Many interesting problems in membrane and membrane-protein biophysics occur on time- and length-scales too long to be effectively explored using all-atom molecular dynamics simulations. We are exploring new methods for representing the membrane implicitly, in particular focusing on techniques which will capture effects of membrane composition beyond simple dielectric effects.
• Wide-angle X-ray scattering (WAXS). WAXS is a relatively new technique for exploring membrane structure. We are working to develop better ways to compare simulation results to WAXS experiments, in order to help validate the simulations and interpret the experiments. This work is being done in collaboration with the Nagle Lab at Carnegie-Mellon and Sachs Lab at the University of Minnesota.

Selected Papers

• Lau, P.-W., Grossfield, A., Feller, S. E., Pitman, M. C., Brown, M. F. Dynamic structure of retinal inverse agonist of rhodopsin probed by molecular dynamics, J. Mol. Biol. 2007, 372, 906-917 pdf
• O'Neil, L. L., Grossfield, A., Wiest, O. Computational Investigation of the Base Flipping of the Thymine Dimer in Duplex DNA, J. Phys. Chem. B, 2007, 111, 11843-11849 pdf
• Grossfield, A., Feller, S. E., Pitman, M. C. Convergence of molecular dynamics simulations of membrane proteins, Proteins: Struc. Func. Bioinf., 2007, 67, 31-40 pdf
• Martínez-Mayorga, K., Pitman, M. C., Grossfield, A., Feller, S. E., and Brown, M. F. Retinal counterion switch mechanism in vision evaluated by molecular simulation, J. Am. Chem. Soc., 2006, 128, 16502-16503 pdf
• Jiao, D., King, C., Grossfield, A., Darden T. A., Ren, P. Simulation of Ca2+ and Mg2+ solvation using Polarizable Atomic Multipole Potential, J. Phys. Chem. B, 2006, 110, 18553-18559 pdf
• Grossfield, A., Feller, S. E., Pitman, M. C.. Contribution of omega-3 fatty acids to the thermodynamics of membrane protein solvation, J. Phys. Chem. B, 2006, 110, 8907-8909 pdf
• Grossfield, A., Feller, S. E., Pitman, M. C., A role for direct interactions in the modulation of rhodopsin by omega-3 polyunsaturated lipids, Proc. Nat. Acad. Sci. USA, 2006, 103, 4888-4893 pdf
• Pitman, M. C., Grossfield, A., Suits, F. and Feller, S. E., Role of cholesterol and polyunsaturated lipids in lipid-protein interaction: molecular dynamics simulations of rhodopsin in a realistic membrane environment, J. Am. Chem. Soc., 2005, 127, 4576-4577 pdf