Thanks Chris Neale.
Before I ask any questions, I'll read your latest paper.
2017-04-06 16:16 GMT-03:00 Chris Neale <candrewn.gmail.com>:
> Diffusion along the US order parameter, computed from US, is almost always
> going to over-estimate the diffusion rate if there are any hidden free
> energy barriers (i.e., dG barriers orthogonal to your US order parameter),
> which there very often are. It's likely that the dehydration cost of those
> two zwitterionic groups on your solute is higher than the cost to deform
> the bilayer and allow hydration of your solute while it's near the bilayer
> center. If that's true, then you're going to run into the common orthogonal
> barrier near the bilayer center which involves flipping the hydrating
> defect from one side of the bilayer to the other. Your US dG profile and
> diffusion tell you nothing about this so you will underestimate the mean
> time required to cross the bilayer.
>
> Chris.
>
> On Thu, Apr 6, 2017 at 1:01 PM, Fabrício Bracht <fabracht1.gmail.com>
> wrote:
>
> > Hi.
> > I've been doing umbrella sampling simulations of a molecule going across
> a
> > POPC bilayer and would like to ask a few questions. First let me describe
> > what I've done so far. I'll be discussing about only one of the molecules
> > I've worked on, since all others follow the exact same protocol.
> > First I generated a lipid bilayer using CHARMM gui. Then I inserted the
> > molecule in substitution from a couple of water molecules. Then I ran
> > minimization, heating, equilibration using the the amber lipid tutorial
> as
> > a guideline. After that, I ran 250 ns of equilibration. My membrane is
> > composed of 120 POPC molecules. The crossing molecule is the
> > 5-methyl-2,4-dinitrophenol. When I started this work, I found this
> tutorial
> > online :
> > https://github.com/callumjd/AMBER-Umbrella_COM_restraint_
> > tutorial/blob/master/README.md
> > Which was very useful. I would like to take this opportunity to thank
> > Callum Dickson for the tutorial and discussion within. Ok, so, moving on.
> > The tutorial also listed 2 very interesting papers.
> > http://pubs.acs.org/doi/abs/10.1021/ct2009208 and
> > http://pubs.acs.org/doi/abs/10.1021/ct200316w
> > And so, I decided to extract the umbrella windows from the 250ns
> > simulation, and not from a pulling simulation, as was my plan earlier.
> > I extracted 150 z position frames, according to the distance between the
> > COM of the molecule and the COM of the POPC nitrogens. These ranged from
> > -35 to +35 angstrom. I then set the 150 distance restrain files spacing
> > them equally using numpy.linspace. You might be wondering why I chose 150
> > and not 140. Well, you see, there was some slight miscalculation
> regarding
> > the size of the simulation box. The original idea was to use 0.5 angstrom
> > spacing and the original box (from charmm gui) would give me a range from
> > roughly -37.5 to +37.5.....so...continuing...
> > I ran about 30 ns of equilibration with a z-position restrain for each
> > window (some windows required more time and some required less). After
> that
> > I ran 15 ns of production run (using the same z-restrain). Then I checked
> > if the distance distribution histograms overlayed (nice overlay,
> indeed). I
> > spaced the distout file samples every 10 md steps. I discarded the first
> 5
> > ns and performed wham on the last 10 ns using positions from z axis only.
> > I used different block sizes (within the 10ns production window) in order
> > to check for convergence, using the final PMF as the convergence
> parameter.
> > I am not sure that this is the best convergence criteria, but I was able
> to
> > see that windows larger than 3 ns had an average PMF that differed very
> > little (less than 0.01 for some z-points). This was a bit time consuming,
> > but it enabled me to have some idea about the accuracy of the final PMF.
> > Ok, now it comes to what I really wanted to discuss. Within the tutorial,
> > there are a few scripts that enabled me to calculate the diffusion and
> > permeability coefficient of the molecule.
> > The problem is that the final value I get for the permeability
> coefficient
> > is a bit large (for my taste, at least). And I was wondering If I did
> > anything wrong. I get as final results,
> > Reff: 0.0620777958588 Peff: 16.1088193639 cm/s
> > If you like, I can gladly share any data you need.
> > I'm not sure if I can attach graphs here, I'll try anyway. The first one
> > should be the diffusion coef values in cm^2/s. The second should be the
> > PMF. Note that it is not perfectly symmetrical because I used the entire
> > z-coordinate across the membrane in order to calculate it. I thought
> about
> > averaging the two halves and mirroring it, like Callum did in the
> tutorial,
> > but though about asking someone first.
> >
> > Thank you
> > Fabrício Bracht
> >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
> >
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Thu Apr 06 2017 - 13:30:02 PDT
