Computer Prediction of pKa Values in Small Molecules and Proteins

Accurately determining the acid dissociation constants (Ka or their logarithmic form, pKa) of small molecules and large biomolecules has proven to be pivotal for the study different biological processes and developing new drugs. This Viewpoint summarizes some of the most common methodologies and recent advances described for pKa prediction using computational techniques when experimental values are not easily accessible such as in proteins and/or for the screening of large libraries of new compounds.