[gmx-users] restraints in PMF (Justin's tutorial)

[Justin A. Lemkul]

Rebeca García Fandiño wrote:
> Hello,
> I am trying to obtain the PMF from Umbrella Sampling of the process of 
> separating two monomers of a dimer, following Justin 's tutorial
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html
> 
> I have done the Umbrella Sampling simulations without using any 
> restraints in any of the monomers, however, I can see that they move and 
> gyrate so that although the c.o.m are separated from each other, there 
> are parts of both interacting, in such way that they are not separated 
> as they should be.
> 
> Would it be correct if I apply restraints to both monomers in all the 
> Umbrella Sampling simulations?. I have seen that in Justin's tutorial 
> they applied restraints to one of the chains, but in my case I think I 
> will need to restrain both of the units. Would that be correct for the 
> PMF calculation?
> 

There are no position restraints applied during the umbrella sampling 
simulations.  They are unnecessary.  The umbrella potential is itself a 
restraint to maintain COM separation.

If parts of your proteins are interacting, you simply haven't fully separated 
your monomers and you need to create configurations with greater COM separation. 
  If you apply position restraints to fit some notion that your monomers 
shouldn't interact at certain distances, then you're applying an unnatural (and 
potentially incorrect) bias, causing the PMF to converge incorrectly.

-Justin

> Thanks a lot in advance.
> 
> Rebeca.
> 
>  > Date: Mon, 20 Jun 2011 17:03:56 -0400
>  > From: jalemkul at vt.edu
>  > To: regafan at hotmail.com
>  > CC: gmx-users at gromacs.org
>  > Subject: Re: doubt about your Umbrella Sampling tutorial
>  >
>  >
>  >
>  > Rebeca García Fandiño wrote:
>  > > Dear Justin,
>  > > my name is Rebeca and I am a postdoctoral student in Santiago de
>  > > Compostela University. Sorry for disturbing you to your personal 
> mail, I
>  > > have tried to post to the Gromacs-list first, but I did not get any 
> answer.
>  >
>  > I was traveling and not paying much attention to messages across the 
> list. I
>  > will CC this reply to the list in the hopes that it is useful to 
> others, as well.
>  >
>  > > I am trying to obtain the PMF from Umbrella Sampling of the process of
>  > > separating two monomers of a dimer, following your tutorial, and I 
> have
>  > > a pair of doubts:
>  > >
>  > > 1)In this tutorial the generation of configurations is done using a 
> .mdp
>  > > file for pulling one chain from another, but is it possible to 
> generate
>  > > the configurations for Umbrella Sampling "by hand", I mean, 
> changing the
>  > > z coordinate of the monomer I want to move, then solvating and then
>  > > minimizing these configurations? Is there any problem with this 
> protocol
>  > > for the obtaining of the configurations?
>  > >
>  >
>  > No problem at all. The tutorial is but one possible method.
>  >
>  > > 2) I have noticed that you use restraints in the md_umbrella.mdp 
> for the
>  > > fixed chain. Is that correct? I can understand the restraints in the
>  > > pulling simulations for generate starting configurations, but once you
>  > > have the configurations, is is necessary to restrain one part of the
>  > > system?
>  > >
>  >
>  > Not usually. The tutorial presents a special case.
>  >
>  > > Thanks a lot in advance for your help with this topic, and thank you
>  > > very much also for publishing this interesting tutorial. There was
>  > > nothing useful until that for Umbrella Sampling with Gromacs 4.0, so I
>  > > think it is more than wellcome for all Gromacs users!
>  >
>  > Glad they're useful :)
>  >
>  > -Justin
>  >
>  > > Best wishes,
>  > > Rebeca.
>  > >
>  > > Dr. Rebeca García Fandiño
>  > > Department of Organic Chemistry and Center for Research in Biological
>  > > Chemistry
>  > > and Molecular Materials
>  > > Santiago de Compostela University
>  > > E-15782 Santiago de Compostela (Spain)
>  > > e-mail: rebeca.garcia.fandino at usc.es
>  > > Phone: 34-981563100 ext 15760
>  > >
>  > >
>  > >
>  > >
>  > >
>  > >
>  > >
>  >
>  > --
>  > ========================================
>  >
>  > Justin A. Lemkul
>  > Ph.D. Candidate
>  > ICTAS Doctoral Scholar
>  > MILES-IGERT Trainee
>  > Department of Biochemistry
>  > Virginia Tech
>  > Blacksburg, VA
>  > jalemkul[at]vt.edu | (540) 231-9080
>  > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>  >
>  > ========================================
> 

-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================