COMPUTING IONIZATION STATES OF PROTEINS WITH A DETAILED CHARGE MODEL

A convenient computational approach for the calculation of the pK(a)s of ionizable groups in a protein is described. The method uses detaile d models of the charges in both the neutral and ionized form of each i onizable group. A full derivation of the theoretical framework is pres ented, as are details of its implementation in the UHBD program. Appli cation to four proteins whose crystal structures are known shows that the detailed charge model improves agreement with experimentally deter mined pK(a)s when a low protein dielectric constant is assumed, relati ve to the results with a simpler single-site ionization model. It is a lso found that use of the detailed charge model increases the sensitiv ity of the computed pK(a)s to the details of proton placement. (C) 199 6 by John Wiley & Sons, Inc.