Computation of protein pK’s values by an integrated density functional theory/Polarizable Continuum Model approach

摘要: This paper describes the extension of our computational strategy for pK predictions small molecules to large solutes. The basic tool results from coupling quantum mechanical methods rooted in density functional theory with most recent version Polarizable Continuum Model. However, a third level is introduced, which includes solute regions far reactive center, are described at simplified level. partition, together implementation fast cavity generation, powerful iterative solvers, and multipole technology, allows us tackle solutes dimension protein. problems perspectives this methodology analyzed special reference behavior different Model versions on challenging playground represented by pK’s histidine residues occurring human prion