H++ in more detail. The server allows both experts and novices to quickly obtain estimates of pKs as well as other related characteristics of bio-molecules such as isoelectric points, titration curves, and energies of protonation microstates. It also automates the tedious process of preparing the input files for typical molecular dynamics simulations. Protons are added to the input structure according to the calculated ionization states of its titratable groups at the user-specified pH; the output structure is in the PQR (PDB + charges + radii) format. In addition, corresponding coordinate and topology files are generated in the format supported by the molecular modeling package AMBER. Several other useful calculations are performed. The server is intended for a broad community of biochemists, molecular modelers, structural biologists, and drug designers; it may also be used as an educational tool in biochemistry courses.

Citations. To acknowledge the use of the server in a publication you may list its web address http://biophysics.cs.vt.edu/H++ and cite these articles:

1. Ramu Anandakrishnan, Boris Aguilar and Alexey V. Onufriev, "H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulation", Nucleic Acids Res., 40(W1):W537-541. (2012).

2. Myers J, Grothaus G, Narayanan S, Onufriev A, "A simple clustering algorithm can be accurate enough for use in calculations of pKs in macromolecules", Proteins, 63, 928-938 (2006).

3. Gordon JC, Myers JB, Folta T, Shoja V, Heath LS and Onufriev A., "H++: a server for estimating pKas and adding missing hydrogens to macromolecules", Nucleic Acids Res. Jul 1;33:W368-71. (2005).

To reference the basic methodology that H++ is based upon, you may cite one of the pioneering works by Don Bashford, such as pKa of Ionizable Groups in Proteins: Atomic Detail from a Continuum Electrostatic Model. by D. Bashford and M. Karplus; Biochemistry, 29 10219--10225, 1990. More references can be found in the Anandakrishnan et al. publication above.

Please also specify the H++ version used.
This is an upgarded (4.0) version. Please click here for a list of the key upgrades.

Acknowledgement. In addition to the authors listed in the above publications, Igor Tolokh, Senior Research Scientist, Virginia Tech, contributed to the development and maintenance of H++.