pKa values of ionizable groups are based on their intrinsic proton affinities in combination with their environments. Shifts in pKa's from intrinsic values, e.g. molecules in solution, can occur in the wide range of environments of various polarities as those offered by proteins. It is generally accepted that additive force fields largely lack the ability to accurately model the full range of polar environments in proteins, which may, in part, be the underlying cause for error in pKa estimates based on free energy calculations. Using pKa as an end-point observation, we determine whether a polarizable model can offer a more accurate prediction of pKa shifts. Presented are the first explicit-solvent calculations of side-chain pKa's for Asp, Glu, and His in Ribonuclease A using the CHARMM classical Drude polarizable force field. Comparisons with the CHARMM additive force field are also presented.

pKa calculations of protein side chains in explicit solvent using the classical drude polarizable force field

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.