H++

H++ is a software tool designed to facilitate the prediction of protonation equilibrium pK constants of macromolecules based on atomic resolution Protein Data Bank structures. The tool automates the process of computing pK values of ionizable groups in macromolecules and adding missing hydrogen atoms according to the specified pH of the environment. This feature enables both experts and novices in the field of biochemistry, molecular modeling, structural biology, and drug design to obtain quick and accurate estimates of pKs as well as other related characteristics of biomolecules such as isoelectric points, titration curves, and energies of protonation microstates.

Apart from its primary function, H++ also provides a set of tools useful for the analysis of electrostatic-related molecular properties. The completed structure can be outputted in several common formats such as PDB, PQR, and AMBER inpcrd/prmtop, making it accessible to a broad community of biochemists, molecular modelers, structural biologists, and drug designers.

The software tool also adds protons to the input structure based on the calculated ionization states of its titratable groups at the user-specified pH, and the output is in the PQR (PDB + charges + radii) format. Corresponding coordinate and topology files are also generated in the format supported by the molecular modeling package AMBER.

In addition to its practical applications, H++ can also serve as an educational tool in biochemistry courses. Its user-friendly interface and automation of complex processes help students learn and understand concepts related to electrostatic-related molecular properties and protonation equilibrium pK constants in a more efficient and effective manner.