From: Richard Law (rlaw_at_llnl.gov)
Date: Fri Nov 09 2007 - 17:43:07 CST
It's all an empiracal force-field so arguably it's all "fudged"! ;)
Science is about learning new things, yes, but trying to do good science
will have the side effect of pleasing reviewers and getting your science
On Nov 9, 2007 2:31 PM, Richard Wood <rwoodphd_at_yahoo.com> wrote:
> Isn't this just "fudging" results? It appears to me that you're just
> changing your results so they fit experimental ones by using one method to
> equilibrate, and then another to do your production run. I thought science
> was about learning new things, and not "pleasing" reviewers.
> I would think one would want to do equilibration using the same method
> that one does for the production run, as I would think this would be one
> thing that reviewers would be more concerned about than one's area per
> lipid. I would also think that if the area per lipid shrinks, one could
> start with a larger lipid so that when it shrinks during equilibration, it
> would be close to the "correct size".
> Richard L. Wood, Ph. D.
> University of Minnesota
> Dept. of Medicinal Chemistry,
> College of Pharmacy
> 717 Delaware St. SE
> Minneapolis, MN 55414-2959
> ----- Original Message ----
> From: Himanshu Khandelia <hkhandel_at_memphys.sdu.dk>
> To: JC Gumbart <gumbart_at_ks.uiuc.edu>
> Cc: Karol Kaszuba <karol.kaszuba_at_moskit.uwm.edu.pl>; namd-l_at_ks.uiuc.edu
> Sent: Friday, November 9, 2007 1:57:10 PM
> Subject: Re: namd-l:
> My take:
> JC is mostly right. For pure membranes, NPT will not work with the charmm
> forcefield, because it was parameterized at a time when constant surface
> tension ensembles were being used for bilayers. I understand that the
> CHARMM development team is working on the problem.
> With a transmembrane protein, the area will still shrink, but slowly,
> because the protein presents a relatively rigid barrier. The larger your
> system (and the larger your protein), the slower the rate at which the
> area shrinks.. If, for example, you are simulating a 100,000 atom system
> for 30 ns at NPT, the area will shrink less than 5-10%, which is
> acceptable in general, at least for purposes of manuscript review, as well
> as for the purposes of the validity of the simulation. On the other hand,
> the area shrinks 10-20% for a 30000 atom system in 40 ns, which is
> significant, and is a problem.
> If using NPAT, the area of the protein can be done using several ways. One
> of them is to use Benoit Roux original scheme which is documented in the
> CHARMM distribution (in the support/membrane section). There is a simple
> script which reads in a pdb file and comes up with a cross sectional area
> profile for a peptide. It can be extended to work for larger protein.
> There are similar grid-based approaches one can look up in recent
> As for the publications not reporting the area per lipid issue in
> protein-membrane simulations using NPT charmm, my personal opinion is
> 1. either the authors are aware of the shrinking membranes in
> protein-membrane simulations, but chose to push the issue under the
> carpet because it is either insignificant and the protein is more
> interesting, or because too much simulation time is at stake.
> 2. The authors are unaware of the problem completely !
> My suggestion:
> If you are just starting, (do not have 6 odd months of simulation time at
> stake), use NPAT, especially if your system is not too big. Just make sure
> that you have a nicely equilibrated system at the right area per lipid. At
> least you will be proud that you used the right methods.
> Of course, all of the above discussion is redundant if you choose to use
> GROMACS, where NPT is the recommended choice, and leads to the right area
> per lipid for most lipids.
> Good luck !
> Himanshu Khandelia, PhD (Chemical Engineering),
> Research Assistant Professor (Postdoc),
> MEMPHYS, Center for BioMembrane Physics: www.memphys.sdu.dk
> University of Southern Denmark (SDU)
> Campusvej 55, Odense M 5230, Denmark
> Phone: +45 6550 3510, +45 2398 7972
> Fax: +45 6550 4048
> email: hkhandel_at_memphys.sdu.dk,
> WWW: www.memphys.sdu.dk/~hkhandel <http://www.memphys.sdu.dk/%7Ehkhandel>
> On Fri, 9 Nov 2007, JC Gumbart wrote:
> > Here is my thinking on the issue. Someone please correct me if I'm
> > The most accurate way is to simulate at NPAT with the appropriate area
> > lipid, although, when simulating with a protein, I don't think it's
> > how to calculate a precise area/lipid. I think many of us get away with
> > because we are not interested in the behavior of the membrane anyway, as
> > as it keeps the protein "happy"; it may not be worth the trouble to find
> > optimal area. This is assuming your area stabilizes though, which
> > it may not (it can shrink a lot in some cases). Then you will certainly
> > to use constant area.
> > On Nov 8, 2007, at 6:00 AM, Karol Kaszuba wrote:
> > > Hello,
> > >
> > > Based on the literature and previous posts I found that CHARMM
> > > does not yield the correct
> > > bilayer geometry in NPT ensemble, however there are many articles in
> > > we can find membrane-protein
> > > simulation in NPT and no one mentions about the problems with bilayer
> > > structure - so I am little
> > > confused - can I use the CHARMM forcefield (release c32b1) to
> simulate POPC
> > > membrane in NPT or
> > > do I have to use NPgamma(surface tension)T or NPAT ?
> > >
> > > Thank you in advance,
> > >
> > > Regards,
> > >
> > > Karol
> > >
> > >
> > >
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