H++: a server for estimating pKas and adding missing hydrogens to macromolecules

The structure and function of macromolecules depend critically on the ionization (protonation) states of their acidic and basic groups. A number of existing practical methods predict protonation equilibrium pK constants of macromolecules based upon their atomic resolution Protein Data Bank (PDB) structures; the calculations are often performed within the framework of the continuum electrostatics model. Unfortunately, these methodologies are complex, involve multiple steps and require considerable investment of effort. Our web server http://biophysics.cs.vt.edu/H++ provides access to a tool that automates this process, allowing both experts and novices to quickly obtain estimates of pKs as well as other related…