Histidine in continuum electrostatics protonation state calculations


  • The authors state no conflict of interest.


A modification to the standard continuum electrostatics approach to calculate protein pKas, which allows for the decoupling of histidine tautomers within a two-state model, is presented. Histidine with four intrinsically coupled protonation states cannot be easily incorporated into a two-state formalism, because the interaction between the two protonatable sites of the imidazole ring is not purely electrostatic. The presented treatment, based on a single approximation of the interrelation between histidine's charge states, allows for a natural separation of the two protonatable sites associated with the imidazole ring as well as the inclusion of all protonation states within the calculation. Proteins 2011; © 2011 Wiley-Liss, Inc.