Charge-charge interactions are the primary determinants of the pK values of the ionizable groups in Ribonuclease T1

Coulomb's law and a finite difference Poisson-Boltzmann based analysis are used to predict the pK values for 15 ionizable side chains (6 Asp, 6 Glu and 3 His) in ribonuclease T1. These predicted values are compared to the measured pK values to gain insight into the most important factors that influence the pK values of the ionizable groups in proteins. Charge-charge interactions are clearly the most important factor that determines the pK values of most ionizable groups in ribonuclease T1. However, pK values can be shifted by several pK units by the Born self energy associated with burying ionizable groups and by favorable intramolecular hydrogen bonding. (C) 2002 Elsevier Science B.V. All rights reserved.