Re: how to visualize an alchemical FEP transformation??

From: Chris Harrison (charris5_at_gmail.com)
Date: Thu Oct 20 2011 - 18:02:32 CDT

Bruno,

VMD does not display the "vanishing" or "appearing" of FEP atoms. If
you look at the energies from the fepout file you can (hopefully) see
that the vanishing/appearing (let's call it the perturbation) is
occurring. In addition, at the top of the namd log file the lambda
value of the FEP atoms is written out for each NAMD run at a given
lambda value:

"FEP CURRENT LAMBDA VALUE <your alchLambda value> "
"FEP COMPARISON LAMBDA VALUE <your alchLambda2 value> "

Hope this helps.

Best,
Chris

--
Chris Harrison, Ph.D.
Theoretical and Computational Biophysics Group
NIH Resource for Macromolecular Modeling and Bioinformatics
Beckman Institute for Advanced Science and Technology
University of Illinois, 405 N. Mathews Ave., Urbana, IL 61801
char_at_ks.uiuc.edu                          Voice: 773-570-0329 
http://www.ks.uiuc.edu/~char              Fax:   217-244-6078
Bruno Luís Pinto de Oliveira <boliveira_at_itn.pt> writes:
> Date: Thu, 20 Oct 2011 21:19:38 +0000
> From: Bruno Luís Pinto de Oliveira <boliveira_at_itn.pt>
> To: Chris Harrison <charris5_at_gmail.com>
> CC: "namd-l_at_ks.uiuc.edu" <namd-l_at_ks.uiuc.edu>
> Subject: RE: namd-l: how to visualize an alchemical FEP transformation??
> 
> Dear Chris,
> 
> > Let's see what we can figure out about your problem; but I'm not
> > entirely sure I understand your description, ie what are the arms, core
> > etc.  As I understand you have a protein containing Re(CO)3 and you
> > perform an FEP in which the *entire* Re(CO)3 is made to "vanish."  Is
> > this correct?
> 
> I published the thermodynamic cycle of my transformation here:
> 
> http://www.boliveira.com/NAMD.html
> 
> Experimentaly, what we observed was that the ligand has less affinity for the enzyme when compared with the Re metal complex. Coordenation of the Re(CO)3 core by the ligand improves the affinity.
> 
> I did docking and MD simulations to get an insight into the structural parameters of the Re(CO)3 core that are responsible for the increased inhibitory effect (the iNOS have a rich polar and charged binding pocket, it makes sense).
> 
> Now I am trying to do FEP to "reproduce" the experimental results. I did the set up such that the Re(CO)3 core vanished.
> 
> I was guessing that during the simulation the amines/ "arms" that are coordenated to the Rhenium turn flexible and interact with the protein after the disappearing of the Re(CO)3 (I understand that is not easy to visualize what I mean).
> 
> My problem is that when I open the simulation with the VMD the rhenium core did not disappear along the simulation (I loaded the .psf and the .dcd written during the simulation)
> 
> I was trying to understand if I should see the Re(CO)3 core "really" disappearing during the simulation or if it is still there but not interact with the protein?? 
> 
> or if I am missing something and I  did not set up the FEP correctly (Although the foward and bacward directions converged).
> 
> Thank you lot...
> 
> Bruno
> 
> I understand it´s not easy to give me an answer ...
> ________________________________________
> De: Chris Harrison [charris5_at_gmail.com]
> Enviado: quinta-feira, 20 de Outubro de 2011 21:21
> Para: Bruno Luís Pinto de Oliveira
> Cc: Axel Kohlmeyer; namd-l_at_ks.uiuc.edu
> Assunto: Re: namd-l: how to visualize an alchemical FEP transformation??
> 
> Bruno,
> 
> Let's see what we can figure out about your problem; but I'm not
> entirely sure I understand your description, ie what are the arms, core
> etc.  As I understand you have a protein containing Re(CO)3 and you
> perform an FEP in which the *entire* Re(CO)3 is made to "vanish."  Is
> this correct?
> 
> You then go on to speak of "arms" that are coordinated to the Re(CO3).
> What are these arms?  And have you added bonded terms describing their
> coordination to the Re(CO3)?
> 
> 
> Best,
> Chris
> 
> 
> --
> Chris Harrison, Ph.D.
> Theoretical and Computational Biophysics Group
> NIH Resource for Macromolecular Modeling and Bioinformatics
> Beckman Institute for Advanced Science and Technology
> University of Illinois, 405 N. Mathews Ave., Urbana, IL 61801
> 
> char_at_ks.uiuc.edu                          Voice: 773-570-0329
> http://www.ks.uiuc.edu/~char              Fax:   217-244-6078
> 
> 
> Bruno Luís Pinto de Oliveira <boliveira_at_itn.pt> writes:
> > Date: Thu, 20 Oct 2011 18:28:13 +0000
> > From: Bruno Luís Pinto de Oliveira <boliveira_at_itn.pt>
> > To: Axel Kohlmeyer <akohlmey_at_gmail.com>
> > CC: "namd-l_at_ks.uiuc.edu" <namd-l_at_ks.uiuc.edu>
> > Subject: RE: namd-l: how to visualize an alchemical FEP transformation??
> >
> > Dear axel,
> >
> > Thank you for your reply. I agree with you. I confess that I still  have some difficulties in understanding what is behind FEP.
> >
> > But that´s why I'm studying the FEP principles and trying to understand my results
> >
> > All of my group work with TI / Amber and nobody can help me.
> >
> > Moreover, in my opinion the NAMD manual is not that well documented in terms of FEP simulations (the only exception is the good tutorial of Chipot et al.)
> >
> > The only possibility I have is asking for "your" help in the forum...
> >
> > My doubt is if the Re(CO)3 core disappear during the FEP simulation the "arms" that are coordenated to it will be free/flexible to interact with the protein??? Or when the Re(CO)3 core is vanished what happens is that only the non-bonded terms are switched off?
> >
> > I know it is a basic question but I can not find an answer...
> >
> > Thank you
> >
> > Regards
> >

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