Re: AW: Dihedrals multiplicity!

From: Kenno Vanommeslaeghe (
Date: Sun Feb 16 2014 - 12:45:16 CST

On 02/16/2014 03:34 AM, wrote:
> Just out of interest: what would you think of a study that embeds a AMBER protein in a CHARMM lipid membrane bilayer?

Depends. If the study is only in a planning/exploratory stage, I would say
"whichever advantage one hopes to get out of of mixing force fields, it's
not worth the uncertainty it casts over the results." If only a few weeks
worth of time had been invested in the mixed force field study, I would
say "one should consider redoing the calculations with consistent force
fields". If restarting is not an option because too much time has been
invested in the simulations and analysis, well, there are a few easy
things that can be done and said to make the results more
credible/palatable to knowledgeable reviewers. Though it also depends on
the purpose of the study; if it explicitly focuses on, for instance,
membrane properties at the interface with the protein, or order/disorder
of the protein induced by the presence of the membrane, then little can be
done to justify mixing force fields.(*) Finally, if you're talking about a
study you came across in the literature, I'd say "interpret with care". On
typical simulation time scales, the inaccuracies induced by the imbalance
of the nonbonded interactions are likely to be not catastrophic.
Properties that are very sensitive to this imbalance, as in the above
examples, are highly suspect. Conversely, phenomena that happen on the
inside of a rigid transmembrane protein may not be affected by the
membrane model much.

(*) I should mention for the sake of completeness that one could
hypothetically just submit a paper and speculate none of the reviewers
will notice the error. Judging by the number of published MD studies with
serious methodological flaws I come across on a monthly basis, there's a
fair chance of getting get away with it. Knowingly doing so would of
course not be a very ethical course of action, and would contribute to the
bad reputation of our field, thus polluting the water for all of us.

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