Dr. Steinbrecher,
Thanks for the quick reply. Actually I'm calculating the relative binding
free energy of REF and NEW. So I'm doing in both in water and protein. So
as you suggest, I probably wanna change the input to something like this:
This is my mdin_min_v0_l05 file:
................
ifsc=1, crgmask='',scmask=':REF.A1',
.................
ifsc=1, crgmask='',scmask=':NEW.B1,B2',
And if i'd like to do the 2-step as a comparison, I should try this:
step1: (here use ref.prm for v1 and new.prm for v0)
................
ifsc=0, crgmask=':NEW.B1,B2',scmask='',
.................
ifsc=0, crgmask=':REF.A1',scmask='',
step2: (here use ref.prm for v0 and new.prm for v1)
................
ifsc=1, crgmask=':REF.A1',scmask=':REF.A1',
.................
ifsc=1, crgmask=':NEW.B1,B2',scmask=':NEW.B1,B2',
I hope I get the direction right. Correct me if I'm wrong. Thanks a lot.
Victor
On Fri, Dec 9, 2011 at 2:37 PM, <steinbrt.rci.rutgers.edu> wrote:
> Hi,
>
> > Problem: changing REF to NEW (actually only one atom is changed in the
> > process)
>
> This is a molecule not bound to anything else in your system I assume? You
> want to go from solvated REF to NEW?
>
> > ifsc=1, crgmask=':REF',scmask=':REF',
> > ...............
> > ifsc=1, crgmask=':NEW',scmask=':NEW',
>
> Two things:
>
> If you set crgmask like this, you change uncharged REF to uncharged NEW.
> This would be the second step of a three-step transformation. For a
> complete single point transformation, leave the crgmask parameter out
> completely. The main point is that appearing/disappearing atoms now *can*
> have charges.
>
> More important though:
>
> REF and NEW will not 'see' each other in this setup. This simulation
> removes one residue completely and replaces it by another. Unless REF and
> NEW are bound to something else, they can move to any part of the system.
> This is a recipe for disastrous convergence problems, like people see in
> absolute binding energy TI calculations. I think it might be better to
> make parts of REF and NEW common atoms, if they are similar in any way, or
> to introduce restraints (but take them into account correctly for total
> dG, check B. Roux papers on this, for example).
>
> Kind Regards,
>
> Thomas
>
> Dr. Thomas Steinbrecher
> formerly at the
> BioMaps Institute
> Rutgers University
> 610 Taylor Rd.
> Piscataway, NJ 08854
>
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Received on Fri Dec 09 2011 - 13:30:02 PST
