Calculating pH and salt dependence of protein-protein binding.
Ionic strength- (or salt-) effects on the protein-protein binding free energy has been included in many computational studies, while comparatively fewer computational studies have looked at the corresponding effect of pH. The pH dependence can be very complex if several groups change protonation state, while the ionic strength dependence usually scales as ln(I), and the main challenge is to predict the magnitude of the correlation. However, there is now very strong indication that pH effects due to binding induced changes in protonation states make a non-negligible contribution to the binding energy of most protein-protein complexes. This observation, together with more efficient pKa prediction methods and the emergence of constant pH molecular dynamics simulations to model the protonation-dependent structural changes will spark more experimental and theoretical work in pH effects on protein-protein binding.
Jensen
Jan H
JH
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark. jhjensen@kemi.ku.dk
D000465:Algorithms; D000595:Amino Acid Sequence; D001665:Binding Sites; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D012492:Salts / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods
D011506:Proteins; D012492:Salts