From: Kenno Vanommeslaeghe (kvanomme_at_rx.umaryland.edu)
Date: Tue Oct 22 2013 - 11:56:59 CDT
Let me start with trying to answer the last question in Revathi e-mail:
no, I don't know of any way to accurately calculate a binding free energy
without having to run simulations for protein (P), ligand (L) and
protein-ligand (PL) complex separately.
It is hard to predict what kind of errors are introduced by
post-processing a CHARMM FF trajectory with the AMBER FF like this. I
guess the worst errors will be canceled out by running all 3 simulations
(PL, P, L) with the same CHARMM-based methodology prior to switching to
AMBER. The remaining errors could be bad, or they could be benign compared
to the approximation of using implicit solvent; I can't easily tell. The
problem could be avoided altogether by using the CHARMM FF with the AMBER
software (which is possible); however, the radii used to generate the
cavity may be optimized for AMBER, which introduces an error that may or
may not be greater than the one discussed above.
If you have access to the CHARMM software, you can do the MM/PBSA analysis
and be free of energy-related as well as file conversion issues, which
would seem to be preferable.
On 10/22/2013 06:01 AM, Jason Swails wrote:
>
>
>
> On Tue, Oct 22, 2013 at 5:21 AM, Peter Jones <pm-jones_at_bigpond.com
> <mailto:pm-jones_at_bigpond.com>> wrote:
>
> Dear Rethvi,
>
> I did this by converting the NAMD-generated dcd trajectory to AMBER
> format using the software Simulaid. Then you just prepare the
> appropriate AMBER topology and parameter files, and use the AMBER
> MM/PBSA protocols to analyse your trajectory. There might be issues
> here regarding artefacts or inaccuracies due to differences in the
> forcefields, I couldn't comment on that, but the results I got made
> very good sense. Converting the trajectory was no laughing matter
> either, and whichever way you go you're probably going to have to just
> dig into the errors until you get rid of them,
>
>
> For what it's worth, the AmberTools program that performs MM/PBSA analyses
> can read DCD files natively, so there's no need to convert them. The
> tricky part is getting the topology file if you are starting with
> CHARMM-based files.
>
> Hope this helps,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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