I'm trying to build a topology of a protein using GROMACS. The pdb file do not include coordinates of hydrogen atoms. So I was wondering how to assign appropriate protonation states for each residue. I have already researched and beside multiple suggestions (H++, propka, Karlberg+, MCCE, GROMACS internal utilities, use number and geometry of hydrogen bonding, experimental data) it is mentioned to assess the environment of a residue manually to get an idea of its protonation.
My questions gears toward criteria one would apply in order to assess the influence of the environment and how to rationalize protonation states from these.
Here some of my ideas
- Residue should be solvent accessible to protonate/deprotonate
- Adjacent residues of opposite strain (B/AH) could facilitate protonation/deprotonation
Especially the distinction between histidin's protonation states (HIE,HID,HIP) seems quite cumbersome to my as well as the occurrence of tyrosine phenolate.
I would appropriate very much everyone sharing. I'm also curious your general approach to this issue as well as you best practice/workflow engaging.