[gmx-users] SARS-CoV-2 main protease with ligand from acpype, but converting to vsites?

[Bjorn Wesen]

Hi list, I have a working sim of the solvated SARS-CoV-2 main protease
dimer from

https://www.rcsb.org/structure/6Y84

using amber99sb-ildn and pdb2gmx-generated vsites for speed, and wanted to
proceed by adding some of the various proposed inhibitor ligands to the sim
for further workflow testing, for example, this one:
"COCCOc1cc(C(=O)N=c2[nH][nH]c(C)c2-c2ccc(Cl)cc2)ccn1".

So I made a pdb of this and generated a .gro and .itp through one of the
online Acpype servers (the one at http://bio2byte.be/acpype ), but there is
no option to generate gmx vsites for getting rid of the hydrogen
bond-angles so I simply assume the result will blow up when running with
the longer timesteps the rest of the sim now uses.

I found a 5 year old post on this list with the same problem, with this
advice from Justin:
https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users/2015-October/101732.html


"At present, the simplest way forward is to take the information you have
in your
ligand topology from acpype and create an .rtp entry, then allow pdb2gmx to
process the whole thing and build the virtual sites on the ligand."

I was wondering, is this still the recommended method? I'm not
super-knowledgeable in the details of how to port something from the ITP to
the RTP formats. Should I just give up on doing it this way or is it an
"opportunity to learn the details" ;) Or is there a better way. Maybe some
other gmx tool to build the vsites for a ligand without having to go all
the way by creating the rtp stuff.

Also, yes, I could simply give up the vsites and run everything slower.
This is the fallback. Maybe some of these ligands simply won't work well
with these constructions at any rate.

Regards
/Bjorn