Re: Alchemical transformations and DDG of point mutations

From: Jérôme Hénin (jerome.henin_at_ibpc.fr)
Date: Fri Dec 14 2012 - 02:38:45 CST

Last time I checked, memory-optimized builds of NAMD were not able to auto-generate the exclusions. That would be the only case where alchemify is still needed.

Cheers,
Jerome

----- Original Message -----
>
>
>
> This is irrelevant, because Mutator plus Alchemify make sure that
> the correct exclusion list is established so that the end states of
> your
> alchemical transformation never see each other.
>
> This is outdated - recent versions of NAMD (for at least the last
> couple years?) automatically generates the exclusions without the
> need to add them to the psf. I don't believe there's any need for
> Alchemify anymore.
>
>
>
>
> On Dec 13, 2012, at 12:47 PM, Chris Chipot wrote:
>
>
>
> Gianluca,
>
>
> 1) Is it better to use alchemy in NAMD in the FEP or TI mode for this
> type of calculatons?
> Contrary to several extraordinary claims (which have never been
> supported by extraordinary evidences), there is no real advantage
> to use TI over FEP, or the other way around. I would, nonetheless,
> advocate FEP for practical reasons -- you can subsequently use
> parseFEP for your post-analysis, notably get the BAR estimator.
>
>
> 2) You describe that in each FEP calculation, 30 intermediate states
> were considered. Does this mean that the progress of lambda was
> broken down into 30 windows each of 150+150 ps? How many FEP
> simulations did you run in total?
> Yes to the first question. I do not quite get the second -- the
> windows
> are chained and the net free-energy change is the sum of free-energy
> changes in individual strata.
>
>
> 3) Do I need to use AlchDecouple on or off?
> I strongly advocate AlchDecouple off , in particular for solvation
> free-energy calculations, as one simply cannot assume that the
> conformational ensembles in vacuum and in condensed phase
> are identical.
>
>
> 4) The VMD mutator plugin replaces both the wild-type and mutant side
> chains such that both clash with the backbone. If this is a problem,
> I might create the PDB myself and still use the PSF generated with
> VMD.
> This is irrelevant, because Mutator plus Alchemify make sure that
> the correct exclusion list is established so that the end states of
> your
> alchemical transformation never see each other.
>
>
> Sorry, lots of questions. I would appreciate any help on this!
> Hopefully, I was convincing enough that it will stop here!
>
>
> Chris Chipot
>
> --
> _______________________________________________________________________
>
> Chris Chipot, Ph.D.
> Theoretical and Computational Biophysics Group
> Beckman Institute
> University of Illinois at Urbana-Champaign
> 405 North Mathews Phone: (217)
> 244-5711
> Urbana, Illinois 61801 Fax: (217)
> 244-6078
>
> E-mail: chipot_at_ks.uiuc.edu
> Christophe.Chipot_at_edam.uhp-nancy.fr Web:
> http://www.ks.uiuc.edu/~chipot
> http://www.edam.uhp-nancy.fr The light
> shines in the darkness, and the darkness
> has not overcome it.
> John
> 1:5.
> _______________________________________________________________________
>

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