Hi Fanyu,
To my understanding, timerge is a means of improving calculation efficiency
(by not duplicating calculations for common atoms). The biggest efficiency
gains for your proposed simulation is probably by merging the common
protein atoms since these are ~100 residues. I wouldn't worry about the WAT
and Na+ in timerge. Note: in amber20, we also experienced trouble with
timerge when we were trying to merge topologies where the mutated amino
acid wasn't part of the last two protein chains. Workaround was to reorder
the protein chains so that the chains that have the mutations are the last
two protein chains (i.e. I would reorder your pdb so that :22-100 comes
first, then :1-10, then :11-20, then sodium and waters)
For the WAT to Na+ transformation, have you tried the following:
- make sure the oxygen on water and Na+ have the same coordinates.
Include the oxygen and Na+ in the timask (but not scmask) so that their
coordinates are linked
- include the hydrogens on water in the scmask
mike
On Mon, Mar 27, 2023 at 1:14 AM Fanyu Zhao via AMBER <amber.ambermd.org>
wrote:
> Dear Amber users and developers,
>
> I have a question about how to prepare dual-topology file for TI
> simulation when converting charge is involved in the calculation of
> relative binding free energy of protein mutation.
>
> For instance, I'm now trying to mutate an Asp to Ala, which means the
> charge of the TI region is converted from +1 to 0. I find that in some
> paper, the authors will simultaneously change a WAT to Na+ when mutating
> the amino acids.
>
> I was wondering how I can get the dual-topology structure with the above
> method if I'm using timerge module in Parmed. It always gives me error
> messages that I can only merge adjacent residues. Because the WAT lines
> will always be put at the end of the pdb file including both wild-type and
> mutant protein. It's always very far away from the wild type, mutants, and
> chosen Na+ I'm going to merge.
>
> For instance, residue :1-10 is TI region 1 (chain with Asp), :11-20 is TI
> region 2 (chain with Ala), :21 is Na+ (will disappear in the end state),
> :22-100 are other chains, :101-200 is WAT. The WAT I choose to appear in
> the end state is residule :101 that is definitely not adjacent to res
> :1-21.
>
> Thank you for taking the time to read this email!
>
> Best,
> Fanyu
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Received on Mon Apr 03 2023 - 11:00:03 PDT
