Hydrogens 001

I would like to start a discussion on what methods are available to add hydrogens to protein structures.
This is probably something a lot of people require since its crucial for molecular modeling.
I have encountered several difficulties so far:

• Not all residues of a given type have the same pKa and therefore protonation state. How to tell the program so?
• Ionizable residues can be protonated at different positions (Nd or Ne in histidine).

I will check out the various options available and report on my findings.

The people on the PyMOL Mailing list have provided me with the following options for adding hydrogens:

1) Reduce is a little more clever about adding hydrogens:

http://kinemage.biochem.duke.edu/software/reduce.php
It optimizes the histidine flips. It is a published algorithm, rather than the unsophisticated one that pymol uses, which is not really doing any optimization.

2) NAMD2

3) MolProbity (http://molprobity.biochem.duke.edu/index.php?MolProbSID=6b810d461879ca495f8d7898629dc18c&eventID=15)

4) Chimera (UCSF, CA, USA, http://www.cgl.ucsf.edu/chimera/). It is free for academics.

The HIS example you mentioned is explicitly treated in Chimera. It shows you all HIS in your protein and you decide which one will be protonated.

5) PROPKA

6) PyMOL

7) OpenBabel

8) AutoDock

9) PDB2PQR. It can complete missing side chain atoms. Gaps in the backbone can not be fixed, apparently. Also, carbonyl groups terminating a gap and peptide nitrogens on the other terminal are not protonated and therefore open shell.

10) WHAT IF