Re: Accelerated MD in NAMD

From: Thomas Evangelidis (
Date: Thu Nov 07 2013 - 04:32:04 CST

On 7 November 2013 09:09, James Starlight <> wrote:

> Professor Wereszczynski,
> also I've seen the implementation of the aMD to the GPCR system (work of
> I.Tikhonova) where only dihedral boost have been applied to the protein and
> lipids as two separate terms.

The authors state that the boost dihedral potential was applied on the
receptor alone as well as the receptor and lipids together (confusing).
They also did a lot of experimentation with E threshold and alpha
parameters (see Supporting Info) to find the optimal combination that
doesn't distort the secondary structure of the protein too much and does
not perturb the POPC membrane excessively (area per lipid headgroup, lipid
bilayer thickness, etc.)

> Does it means that the transition to the active state of the receptor is
> primarily structural dependent event? (this time you have not used total E
> boost which are influence on the diffusion rates). Doest it takes from the
> assumption that the receptor is fixed in the membrane so we might not take
> into account diffusion ?
> some off-topic- in this paper I've seen interesting methodology when you
> compare MD observations with the distribution of the X-ray structures of
> this receptor (solved in active and inactive states as such reference
> points). My question is in methodology- will it more correct to project
> C-alpha coordinates of X-ray structures onto the Principal modes calculated
> for the MD trajectory or alternatively project MD snapshots onto the
> Principal modes calculated from the ensemble of the X-ray structure ?(!) In
> last case we have robust assumption that X-ray ensemble is the trajectory
> capturing R->R* transition seen in experiment (!) So lowest frequency modes
> gives evidence about possible path of this transition if we have number of
> intermediates. Alternatively in the first case (as has been done in the
> Tikhonova paper) we have assumption that accelerated simulation with the
> artificial boost can be the reference for the monitoring some biological
> event (R->R* transition) so in this case we test X-ray structures (not the
> simulation setup). Which statement would be most probably? Does somebody
> see the implementation of such methodology (projections of the X-ray
> structures onto MD and vice versa) with other proteins ?
> The eigenspace derived from the MD trajectory will be much larger than
that derived from 3 or so X-ray structures. Therefore projecting the the
X-ray coordinates onto the PCs of the MD trajectory makes more sense than
the reverse. The other important detail you have to consider when you
present that heatmap is how much of the variance of the atomic fluctuations
the first two PCs explain. If for example they explain just 30% then it
doesn't make much sense to present it.

> --


Thomas Evangelidis

PhD student
University of Athens
Faculty of Pharmacy
Department of Pharmaceutical Chemistry
157 71 Athens



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