in that case, you'll need to measure the deltaG of wild type to mutant in
the folded state, and also deltaG for wild type to mutant in the unfolded
state. You can't just do the folded state calculation using methods that I
know about. The unfolded state can be difficult to model due to the size of
the water box and also sampling the huge conformational space needed for
the averages to converge. Typically you would need to make some
approximations for the unfolded state calculation.
I suggest searching the literature to find examples of this sort of
calculation. It's at the very edge of what I would consider feasible, and
much will depend on the properties of your particular protein. The methods
can be very challenging, so rather than trying lots of possibilities you
want to look and see what has worked for others and then adapt it to your
needs. I would not suggest taking on a project like calculating the impact
of mutation of folding free energy without doing a literature search first.
Once you decide on methods, then the Amber list will be a great resource
for the technical questions you might have while implementing them.
On Sat, Feb 27, 2016 at 1:48 PM, Mijiddorj Batsaikhan <b.mijiddorj.gmail.com
> wrote:
> Dear Carlos and Rajeswari,
>
> Thank you for your reply. Main point is folding difference between wt and a
> mutant. Thank you again.
>
>
> Batsaikhan
>
> On Sun, Feb 28, 2016 at 1:32 AM, Carlos Simmerling <
> carlos.simmerling.gmail.com> wrote:
>
> > I agree, and in fact I don't think its straightforward to calculate G
> > itself anyway, deltaG is much easier. but again, it really depends on the
> > process for which you want to compare wild type and mutant. there are
> many
> > methods for free energy calculation, and it's hard to recommend one
> without
> > knowing what the actual endpoints are.
> >
> > On Sat, Feb 27, 2016 at 12:11 PM, Rajeswari A. <
> > rajeswari.biotech.gmail.com>
> > wrote:
> >
> > > Please have a look at the following thread. It was suggested that you
> > > cannot compare the G(wt) and G(mutant) directly. But you can compare
> the
> > > delta G from both.
> > >
> > > http://archive.ambermd.org/201511/0167.html
> > > On 27-Feb-2016 6:44 pm, "Carlos Simmerling" <
> carlos.simmerling.gmail.com
> > >
> > > wrote:
> > >
> > > > TI is usually considered to be more accurate, but takes more time to
> > run.
> > > > MMPBSA just requires the MD simulation for each mutant. You could
> start
> > > by
> > > > looking at tutorials A3 and A9.
> > > >
> > > > On Sat, Feb 27, 2016 at 8:02 AM, Mahdieh Hadi <
> mahdieh.hadi.bric.ku.dk
> > >
> > > > wrote:
> > > >
> > > > > Thanks a lot. and which one is more accurate?
> > > > >
> > > > > ________________________________________
> > > > > From: Carlos Simmerling [carlos.simmerling.gmail.com]
> > > > > Sent: Saturday, February 27, 2016 1:48 PM
> > > > > To: AMBER Mailing List
> > > > > Subject: Re: [AMBER] How to analyze mutational free energy
> > difference?
> > > > >
> > > > > this can be done either with TI or by using MD with MMPBSA,
> depending
> > > on
> > > > > the level of accuracy that you need.
> > > > >
> > > > > On Sat, Feb 27, 2016 at 7:46 AM, Mahdieh Hadi <
> > mahdieh.hadi.bric.ku.dk
> > > >
> > > > > wrote:
> > > > >
> > > > > > I have almost the same problem. Which tutorial is suitable for
> > ligand
> > > > > > binding?
> > > > > > ________________________________________
> > > > > > From: Carlos Simmerling [carlos.simmerling.gmail.com]
> > > > > > Sent: Saturday, February 27, 2016 1:39 PM
> > > > > > To: AMBER Mailing List
> > > > > > Subject: Re: [AMBER] How to analyze mutational free energy
> > > difference?
> > > > > >
> > > > > > what is the process for which you want the free energy? ligand
> > > binding?
> > > > > > folding? activation? then we can suggest tutorials for that.
> > > > > >
> > > > > > On Sat, Feb 27, 2016 at 2:34 AM, Mijiddorj Batsaikhan <
> > > > > > b.mijiddorj.gmail.com
> > > > > > > wrote:
> > > > > >
> > > > > > > Dear users,
> > > > > > >
> > > > > > > I want to make mutational free energy difference of protein
> > > structure
> > > > > > > (delta G = G wild-type - G mutant). If you do not mind, please
> > give
> > > > me
> > > > > > > advice, and suggestions of related tutorials.
> > > > > > >
> > > > > > >
> > > > > > > Batsaikhan
> > > > > > > _______________________________________________
> > > > > > > AMBER mailing list
> > > > > > > AMBER.ambermd.org
> > > > > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > > > > >
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Received on Sat Feb 27 2016 - 11:00:04 PST
