Past Event: Oden Institute Seminar

O, Proton(s), Where Art Thou?

Qiang Cui, Department of Chemistry University of Wisconsin, Madison

Abstract

In this talk, I will discuss several topics inspired by our long-term goal of understanding proton pumping in biomolecular systems using theoretical techniques. As stringent tests for the theoretical methods and computational protein model for complex biomolecular systems, pKa calculations are carried out using “brutal-force” QM/MM free energy perturbation methods for titritable amino acids in different protein environments. These include surface-exposed and buried residues in soluable proteins and buried residues in membrane proteins. The magnitude of errors introduced by the lack of electronic polarization in the MM force field, limited accuracy in the QM method, approximations in the solvent boundary condition as well as the impact of sampling are discussed. The calibrated QM/MM method is then applied to analyze the infrared spectra for the proton release group (PRG) in bacteriorhodopsin, and the results provide an alternative explanation for the interesting diffuse band identified experimentally. Finally, if time permits, the mechanism of ATP hydrolysis in myosin will also be briefly discussed as part of the effort to understand mechanochemical coupling in this representative molecular motor, where there are also unexpected features regarding the destination of protons. *Refreshments served at 3:00.