Protonate3D: Assignment of ionization states and hydrogen coordinates to macromolecular structures

A new method, called Protonate3D, is presented for the automated prediction of hydrogen coordinates given the 3D coordinates of the heavy atoms of a macromolecular structure. Protonate3D considers side-chain “flip,” rotamer, tautomer, and ionization states of all chemical groups, ligands, and solvent, provided suitable templates are available in a parameter file. The energy model includes van der Waals, Coulomb, solvation, rotamer, tautomer, and titration effects. The results of computational validation experiments suggest that Protonate3D can accurately predict the location of hydrogen atoms in macromolecular structures.