AMBER Archive (2007)

Subject: Re: AMBER: results from TI

From: Holly Freedman (freedman_at_phys.ualberta.ca)
Date: Tue Oct 23 2007 - 15:29:00 CDT

Hi Thomas and David,
Yes, when I looked at the breakdown of DVDL it is mostly electrostatic, and the van der waals part's
only about -0.5kcal/mol. I'll have to experiment to get better convergence, and I'll let you know.
Thanks,
Holly

> Hi Holly,
>
> be sure to look at the breakdown of the DVDL at the end of the output
> file. I bet most of the 17kcal is 1-4 interactions and electrostatics, and
> only a small part is VDWAALS. Removing a few atoms should result in only
> a few kcal/mol free energy change at most.
>
> Your input files for the sc part look good too at first glance, maybe this
> is really just an issue of sampling. I you do one ns more and a few lambda
> points more, do your results change significantly?
>
> It should be no problem if your middle step transforms between two
> completely arbitrary charges, this will all balance out in the end, but
> try and include the oxygen in the softcore part both in the OH and OMe
> groups to see if you get a similar result.
>
> Regards,
>
> Thomas
>
> Dr. Thomas Steinbrecher
> The Scripps Research Institute
> 10550 N. Torrey Pines Rd.
> San Diego CA 92037, USA
>
> >
> >> Thanks for your response. The value for the LJ component is -17kcal/mol (I had said -16
before but
> >> that was wrong). In fact I looked at this and I didn't equilibrate long enough, so this is one of
my
> >> problems. I suspect the reason that it's so negative is because like I was saying the molecule
has
> >> different charges when different charges have been removed (the magnitudes of solvation free
> >> energies of ions are enormous, eg sodium with one unit of charge is about -77 kcal/mol). So
when I
> >> repeat the calcuations I think I should change the groups being permuted to make them more
> >> neutral; that way the system will be sure to equilibrate reasonable fast. I'll let you know how
this
> >> turns out.
> >
> > Oh, but when you say LJ component, you are still changing charges at
> > the same time, right? I guess this could be a large number.
> >
> > I still think your problem is most likely to be not having enough
> > lambda values, but it's hard to be sure -- I haven't done that many
> > relative free energy calculations. However, my experience has been
> > that just having large charges is not necessarily a problem (although
> > I do prefer to keep the system net neutral).
> >
> > Keep us posted on what you figure out. We have a free energy wiki of
> > sorts at http://www.alchemistry.org which is still rather preliminary,
> > but we're trying to collect some "best practices" information there.
> > If you're up for it, it would be great if you can post any new
> > insights to the wiki
> > (http://www.alchemistry.org/index.php/Best_Practices).
> >
> > Thanks,
> > David
> >
> >
> >> Thanks again,
> >> Holly
> >>
> >>> (1) See about adding more lambda points. In my experience even with
> >>> five point TI for the charging energies one gets significant (i.e.
> >>> ~0.2-0.5 kcal/mol) integration error even when leaving the net charged
> >>> fixed (i.e. for the charging free energy of SPC water in SPC water),
> >>> say roughly a 5-10% error. I could easily imagine that using three
> >>> point integration for something where the magnitude is more than 20
> >>> kcal/mol could give you at least 3 kcal/mol of integration error. 9
> >>> points is also few for the LJ part -- but adding more points won't
> >>> make as big a difference in the total answer since the net LJ
> >>> component is usually fairly small and should be similar for these two
> >>> molecules.
> >>> (2) Maybe send along your values for the LJ component. One would
> >>> expect this to be small (~0.5 kcal/mol?) so if it's not, that would be
> >>> a sign of some sort of problem there.
> >>>
> >>> Thanks,
> >>> David
> >>
> >>
> >>
> >> --
> >> Department of Physics, University of Alberta
> >> Edmonton CANADA
> >>
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--
Department of Physics, University of Alberta
Edmonton CANADA

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