[gmx-users] Re: Re: (dH/dl) calculation
Mauricio Sica
msica at unq.edu.ar
Tue Nov 7 14:31:34 CET 2006
Tanks David
Exactly: I`d want to calculate "dG/dl for some particular component of
the energy". Why? I did 2 FEPs, so I have two Delta_Gs for a mutations in
2 states: folded and unfolded. Both Delta_Gs are positive values. The
difference between them (Delta_Delta_G) is the value I was looking for.
This value agrees with experimental value of Delta_G of unfolding between
2 mutant proteins. Now, I want to know what is stabilizing or
destabilizing each state with respect the other. Analysis of each
component (e.g. Coul-SR:Prot-Prot) is impossible: it happens that I’m
searching a delta_E of < 10 Kcal between a magnitude of 10E6. So I
thought that if I could obtain a <dE/dl> for a component and then
integrate them along lambda (TI method), I could get some idea about its
magnitude.
Mauricio
> Mauricio,
>
> > That was exactly what I wanted to know. From one hand, because I just
> > wanted to know it and, from the other hand, because I think that if I
> have
> > some idea about how this calculus is carried out, I was able to
> estimate a
> > Delta_E for some energy components, for example,
> Coul-SR:Protein-Protein
> > by means of calculating the corresponding <dE/dl> (even when I know
> that
> > the value is not a state function as stated in the Mark & v Gunsteren
> > paper). Maybe I should have started from this point. Is it posible?
>
> I'm sorry, I have no idea what you're asking here. Are you talking
> about trying to calculate a dG/dl for some particular component of the
> energy? That doesn't sound useful, to me, since the components
> generally are all interdependent. And if you are trying to separate
> out the contribution of different components to the total dG/dl, this
> would require source code modifications, in general. Again, if you can
> be more specific about what exactly you want to do (what problem are
> you trying to solve?) people may be able to be more helpful.
>
> David
>
>
> > > Message: 6
> > > Date: Mon, 6 Nov 2006 10:19:05 -0800
> >
> > > Mauricio,
> > >
> > > I'm somewhat confused by your question and notation. However, I
> think
> > > the basic answer is something like this: In molecular dynamics, you
> > > know the Hamiltonian from which you are sampling; call it H(x,p,
> l),
> > > where x denotes all of the positions, p the momentums, and l
> lambda.
> > > This, of course, is closely linked to the potential energy. Anyway,
> at
> > > any snapshot, you can simply take the derivative dH(x,p,l)/dl, and
> you
> > > have dH/dl at that snapshot. This is usually straightforward since
> you
> > > know the dependence of all of the terms in your Hamiltonian on
> lambda,
> > > so you actually have the functional form for dH/dl as well -- so it
> > > just involves taking the appropriate combination of positions,
> > > momentums, etc. This is of course all handled internally by the
> code.
> > > <dH/dl>, then, is just the time-average of dH/dl, which can be
> > > evaluated every step by the code.
> > >
> > > I am not sure if that's helpful at all, as I'm not entirely sure
> what
> > > problem you're having. After all, whenever you do TI calculations
> in
> > > GROMACS, the code gives you back dG/dl (or dH/dl, or dA/dl) for
> every
> > > snapshot in an xvg output file. Are you just confused about how the
> > > code gets this (I think I just answered that above), or are you
> trying
> > > to figure out how to use it? If you're confused about how to use
> it,
> > > try to ask a question that relates to the specific issue you're
> > > confused about.
> > >
> > > Best wishes,
> > > David Mobley
> > > UCSF
> > >
> > >
> > > On 11/5/06, Mauricio Sica <msica at unq.edu.ar> wrote:
> > > > Dear experts
> > > >
> > > > I am doing FEP (thermodynamic integration method) simulations.
> > > > I have a questions about <dH/dl> calculation in GROMACS.
> > > > Take in mind equation 3.77 from the GROMACS 3.3 manual.
> > > > There, dA/dl is calculated as
> > > >
> > > > dA/dl = SS{ (dH/dl) exp()dp dq } / SS{ exp()dp dq = <dA/dl>NVT;l
> }
> > > >
> > > > where SS are doble integrals (sorry for the notation).
> > > >
> > > > My question is: how is (dH/dl) (in the middel-term of the
> equation)
> > > > calculated?
> > > > My idea is that the difference V(L=1)-V(L=0) is calculated for
> every
> > > time
> > > > step (irrespective of the lambda value of the simulation) and
> <dG/dl>
> > > is
> > > > the time average of that difference.
> > > >
> > > > <dG/dl> = < V(L=1)(i)-V(L=0)(i)/1 >
> > > >
> > > > Is this correct?
> > > >
> > > >
> > > > Thanks
> > > >
> > > >
> >
> >
> >
>
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