pKD: Re-designing protein pKa values

Abstract

The pKa values in proteins govern the pH-dependence of protein stability and enzymatic activity. A large number of mutagenesis experiments have been carried out in the last three decades to re-engineer the pH-activity and pH-stability profile of enzymes and proteins. We have developed the pKD webserver (http://polymerase.ucd.ie/ pKa_Design), which predicts sets of point mutations that will change the pKa values of a set of target residues in a given direction, thus allowing for targeted re-design of the pH-dependent characteristics of proteins. The server provides the user with an interactive experience for re-designing pKa values by pre-calculating ΔpKa values from all feasible point mutations. Design solutions are found in less than 10 min for a typical design job for a medium-sized protein. Mutant ΔpKa values calculated by the pKD web server are in close agreement with those produced by comparing results from full-fledged pKa calculation methods. © The Author 2006. Published by Oxford University Press. All rights reserved.