The H++ web server described here automates the process of calculating pKa, protonation states and titration curves of ionizable groups in macromolecules, given an atomic resolution structure as input. In addition, the server generates the properly protonated structures for use in other popular molecular modeling applications, such as MD. The calculations are based on the established continuum electrostatics methodology, which has been successfully used for this purpose over more than a decade. We expect H++ to become a useful tool for the broad biochemical, structural and computational biology community, as well as drug designers. It can also be a useful educational resource.
We thank Grigori Sigalov and Jory Zmuda for useful comments and suggestions. We are also grateful to Yuri Pevzner for the help with testing and to Derek Rountree for the help with incorporating the latest GB model into the MEAD package. Funding to pay the Open Access publication charges for this article was provided by Virginia Tech.
Conflict of interest statement. None declared.