title: pKD: re-designing protein pKa values.
abstract: The pK(a) 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 pK(a) 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 pK(a) values by pre-calculating DeltapK(a) 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 DeltapK(a) values calculated by the pKD web server are in close agreement with those produced by comparing results from full-fledged pK(a) calculation methods.
authors.affiliation: School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Tynan-Connolly
authors.forename: Jens Erik
authors.initials: JE
authors.lastname: Nielsen
mesh_terms: D003196:Computer Graphics; D006863:Hydrogen-Ion Concentration; D020407:Internet; D008958:Models, Molecular; D017354:Point Mutation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012984:Software
chemical_list: D011506:Proteins