[gmx-users] Defining protonation in pdb2gmx input

[Justin Lemkul]

On 5/9/18 9:11 AM, mhuhtala at abo.fi wrote:
> This is continuing a thread from a month ago.
>
>> Quoting Justin Lemkul <jalemkul at vt.edu>:
>
>>> Now I did a bit more testing, and at least renaming ASP to ASPH in 
>>> the input will get me an ASPH in the output, but only the residue 
>>> name, not the hydrogen. So I get a residue named ASPH, but the 
>>> structure is an unprotonated ASP. Is this a bug? Or is pdb2gmx 
>>> expecting to find the hydrogen atom line in the input?
>
>
>> All necessary hydrogens should be reconstructed according to the .hdb 
>> file (for which entries for protonated amino acids exist and are 
>> functional).
>
> Reading the source code of pdb2gmx, that does not seem true. I don't 
> fully understand the code after a quick look, but it seems to me that 
> ASPH and GLUH are always matched to ASP and GLU (if not entered 
> manually), and that the protonation routine is only for HIS. And once 
> pdb2gmx matches ASPH with ASP, it refuses to read the hydrogen atom 
> even if it is in the input (because it wants ASP).
>
>>> This is all using Gromacs 2018 and specifying GROMOS96 54a7, and 
>>> modifying a crystal structure PDB file taken from the PDB, with no 
>>> hydrogens.
>
>> There does appear to be a problem specifically with united-atom force 
>> fields. Both CHARMM and AMBER function correctly, with or without 
>> -ignh. Using any GROMOS variant, with or without -ignh leads to a 
>> problem.
>
> That's not true, actually, as far as I can tell. I did a bit more 
> testing, and ASPH in the input does NOT get protonated for AMBER99 or 
> CHARMM27 either. I tried with 2018.1.
>

AMBER uses ASH and CHARMM uses ASPP. Both of those work; I just 
double-checked.


> The bug I reported earlier (assuming then it was Gromos only): 
> https://redmine.gromacs.org/issues/2480
>
>
There is a problem in automatically detecting provided ASPH, and it 
affects OPLS-AA, too. The topology is correctly written if interactively 
selecting the protonation state via -asp (I confirmed this with both 
OPLS-AA and GROMOS) but otherwise does not work. That may be useful 
information in updating the bug report.

-Justin

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Justin A. Lemkul, Ph.D.
Assistant Professor
Virginia Tech Department of Biochemistry

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