Computational Approaches for Protein pK _a Calculations

Ionizable residues play an essential role in many important biological reactions. The pH-dependent properties of proteins depend on the pK a values of ionizable groups and their resulting protonation states at a given pH. Consequently, it is very important to be able to accurately predict the pK a and understand which factors determine the pK a of ionizable groups in proteins. In this chapter, we discuss pK a determination of ionizable groups in proteins and evaluate a number of computational methods used for pK a predictions.