Re: Accelerated MD in NAMD

From: James Starlight (
Date: Thu Nov 07 2013 - 06:48:45 CST


thanks for suggestions!

1) I also would rise question about precise values of the <Udihe>. As a
test I decide to simulate the same b2a receptor in the 120 lipids bilayer
in cMD (npt conditions, 2ps damping, 310K. all parameters have been taken
from charm-gui). After short simulation I've obtained total <Udihe>=10000
Kcal/mol (2000 for protein and 8000 for lipids).
So my boost should be based onto the E=10000+4*(340+120) <! here I'm not
sure how include lipids so I include just number of lipids > ~ 12000 and
alpha should be ~ 400-500.
 In comparison In Tikhonova paper I found the same values of <Udihe> ~ 1300
kcal/mol for protein and 900 (!) for lipids. Does it meas that my system in
need not for the boost potential at all ? :)

2) About projection. In my example I have 80% variance along 1 PC (here all
structures have been grouped on R and R*) and 20% along other 10 modes
(total 10 x-ray structures= 10 modes). On other hand on MD trajectory I
have only 40% variance of 1 PC ( I didnt notice large-scale conformation
changes on this mode corresponded to the R-> R* transition). Ther fore I
should to project MD ensemble onto PC calculated for the X-ray dataset,
shouldnt it? :)


2013/11/7 Thomas Evangelidis <>

> 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
> Panepistimioupoli-Zografou
> 157 71 Athens
> email:
> website:

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