Re: Fw: Calculating Free Energy Change

From: Shirley Hui (shirleyhui_at_alumni.uwaterloo.ca)
Date: Fri Apr 23 2004 - 13:44:17 CDT

Brian,

Thank you for your clarification.

Yes, in my case, I would consider lambda = 0 as conformation 1 and lambda =
1 as the final conformation.
I did come across the posting you sent me. My impression was that this tool
takes as input a PDB style FEP file and spits out a PSF file which can then
be sent into the *alchemical FEP* of NAMD. See the excerpt below:

"It also needs a FEPfile (as described in the NAMD
manual), stating what atoms belong to the initial and final groups. Given
these, the tool produces a cleaned-up PSF file, that should be suitable for
alchemical FEP with NAMD."

However, my problem does not involve any alchemical transformations of the
molecule. This is what I am assuming...
In the case of alchemical transformations, residues can mutate into other
ones (i.e alanine to glycine etc).
In the case of conformational changes, the molecule is simply undergoing a
conformational change whereby the residues remain the same but the positions
differ.

QUESTION ONE:
Would the alchemcial function be suitable in my case, if there is no
alchemical transformations taking place? Would one of the FEP algorithms
mentioned in the user guide
(http://www.ks.uiuc.edu/Research/namd/current/ug/node33.html) either MCTI or
PMF approach be more suitable?

I intend to create an FEP file with the initial coords corresponding to
lambda = 0 and the perturbed coords corresponding to lambda =1.
Then run the simulation for FEP calculation in NAMD using MCTI or PMF.
***If anyone knows that this is incorrect, please let me know!***

QUESTION TWO:
My final question has to do with clarifying what all the conformational
constraints mean:
http://www.ks.uiuc.edu/Research/namd/current/ug/node33.html#SECTION000973000
00000000000

What is the difference between:
Restraint Specifications (not coupled to pmf calculation) - is this only for
mcti??
Bound Specifications (not coupled to pmf calculation) - is this only for
mcti??
Forcing Restraint Specifications (coupled to pmf calculation) - only for
pmf, related to the restraint potential??

Are there some papers or text books that someone can recommend that I can
read up on this?

Thank you!
shirley

----- Original Message -----
From: "Brian Bennion" <brian_at_youkai.llnl.gov>
To: <namd-l_at_ks.uiuc.edu>
Sent: Friday, April 23, 2004 12:08 PM
Subject: Re: namd-l: Fw: Calculating Free Energy Change

> Hi Shirley
>
> The is the email I was talking about:
>
> http://www.ks.uiuc.edu/Research/namd/mailing_list/namd-l/0746.html
>
> Changing conformations is equivalent to changing morphing from one residue
> to another, so long as the change is only a "perturbation". For
> example changing a proline conformation from cis to trans or vice versa
> probably isn't a "perturbation" but my knowledge here is not great....
>
> In your case lambda=0 is one confromation and lambda=1 is the final
> conformation. Unless I have totally misunderstood your question.
>
> Brian
>
>
> On Thu, 22 Apr 2004, Shirley Hui wrote:
>
> > Thank you for your reply.
> > I searched the list for anything relating to what I wanted to do, but
either I am not looking far back into the archive, or I really don't know
what I am doing!
> > This is the list I am searching:
> > http://www.ks.uiuc.edu/Research/namd/mailing_list/namd-l/
> > Instead I am wondering if doing the following would do what I want.
> > I was thinking of supplying NAMD with an fep file whereby the original
conformation and the coordinates associated with that conformation are in
the PDB-style file with -1.00 ('vanish'). In the same PDB-style fep file I
would also have the coordinates for the perturbed conformation with 1.00
('appear').
> > Then I would run NAMD FEP calculations using this file.
> > My thinking is that the original conformation is changing/perturbing to
the perturbed conformation. Instead of residues vanishing or appearing,
it's the same ones, but in different locations.
> > Does this work - am I on the right track??
> > I'm sorry, I was unable to find the tool that you are referring to
below??
> > Thanks for your insight,
> > shirley
> >
> >
> > >From: Brian Bennion <brian_at_youkai.llnl.gov>
> > >To: Shirley Hui <shirleyhui_at_alumni.uwaterloo.ca>
> > >Subject: Re: namd-l: Fw: Calculating Free Energy Change
> > >Date: Thu, 22 Apr 2004 11:42:46 -0700 (PDT)
> > >
> > >Hi Shirley,
> > >
> > >From the user guide page you supplied it states that your problem can
be
> > >implemented in NAMD.
> > >
> > >Search this list for the description of a tool that creates the FEP
> > >scripts based on two end points.
> > >
> > >Brian
> > >
> > >On Thu, 22 Apr 2004, Shirley Hui wrote:
> > >
> > > > I was wondering if anyone could clarify some things for me.
> > > >
> > > > NAMD's Free Energy Calculator was meant to calculate the free energy
change between various perturbations of a molecule (the perturbations would
be constrained).
> > > > Does anyone know if it is possible to give NAMD two conformations of
the same molecule and then calculate the free energy change between the
two?? Basically I am perturbing a molecule myself and then I want to know
the free energy change between the original conformation of the molecule and
the perturbation I made. If not NAMD are there any other software that can
do this?? If not, I guess I will have to implement my own and I know this
is not a trivial task.
> > > > Thanks for any insight, the examples on the web page on NAMD's Free
Energy Calculator are a bit too in depth or detailed for me at the moment to
fully understand.
> > > > http://www.ks.uiuc.edu/Research/namd/current/ug/node33.html
> > > > thanks,
> > > > shirley
> > > >
> > >
> > >*****************************************************************
> > >**Brian Bennion, Ph.D. **
> > >**Computational and Systems Biology Division **
> > >**Biology and Biotechnology Research Program **
> > >**Lawrence Livermore National Laboratory **
> > >**P.O. Box 808, L-448 bennion1_at_llnl.gov **
> > >**7000 East Avenue phone: (925) 422-5722 **
> > >**Livermore, CA 94550 fax: (925) 424-6605 **
> > >*****************************************************************
> > >
> >
>
> *****************************************************************
> **Brian Bennion, Ph.D. **
> **Computational and Systems Biology Division **
> **Biology and Biotechnology Research Program **
> **Lawrence Livermore National Laboratory **
> **P.O. Box 808, L-448 bennion1_at_llnl.gov **
> **7000 East Avenue phone: (925) 422-5722 **
> **Livermore, CA 94550 fax: (925) 424-6605 **
> *****************************************************************
>
>

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