VMD-L Mailing List

From: Giacomo Fiorin (giacomo.fiorin_at_gmail.com)
Date: Fri May 25 2018 - 08:09:32 CDT

Hi Kelly, ABF, metadynamics, umbrella sampling or any of the other methods
provided in Colvars will only affect directly the atoms that you select,
and never touch the others. If you want water molecules to move, you will
have to define variables that involve them explicitly. In particular,
atoms and molecules are not deleted: that's something you can only do
during system preparation.

As for how each enhanced sampling method goes about sampling the collective
variables space, you should take a look at the literature. These papers
are usually referenced in each tutorial.

Technical information about how to use them in NAMD is here:
http://colvars.github.io/colvars-refman-namd/colvars-refman-namd.html
and here:
https://github.com/Colvars/examples

Lastly, knowing the system that you are looking at, my advice is to look at
what kind of transformations need to occur for this calculation to work.
You have three constriction regions, each of which needs to open to let the
inhibitor molecule pass. Even for smaller movements, some
wetting/dewetting is necessary, which is not always fast. Explicitly
adding or deleting water molecules may give the appearance that you are
sampling wetting/dewetting transitions, but if these don't happen during
simulation the artificial initial conditions bias the results.

Giacomo

On Thu, May 24, 2018 at 1:10 PM, McGuire, Kelly <mcg05004_at_byui.edu> wrote:

> I am preparing to do some ABF calculations with the molecules I sent
> through FFTK by working through the tutorial. I am placing these molecules
> in the influenza A M2 protein to get their free energy profiles in order to
> understand their entry/exit and interactions inside the protein. I will
> have some questions as I work my way through the tutorial. My first one
> is more of a general question on how ABF works. I've done some umbrella
> sampling before, and the way we have done this in the past is create
> multiple input files with the molecule/drug at different positions in the
> protein, delete the waters at the drugs new position, and submit all of
> those jobs to the supercomputer, which as you can imagine is very
> tedious/inefficient. I am wondering though how the ABF set up in NAMD
> handles moving the drug and deleting waters around the drug at the new
> position? For example, say I have the drug starting at one end of the
> protein and we call that position on the reaction coordinate -15 Angstroms,
> and the drug is to be moved to the other end of the protein, call it 15
> angstroms (so, 30 angstroms for the total reaction coordinate), how
> does the part of the colvars script, (width 0.1, lowerboundary -15,
> upperboundary 15), move the drug to the next spot and delete waters around
> it? Is this some kind of a loop that NAMD recognizes to move the drug?
> Thanks!
>
>
> *Kelly L. McGuire*
>
> *PhD Scholar*
>
> *Department of Physiology and Developmental Biology*
>
> *Brigham Young University*
>
> *LSB 3050*
>
> *Provo, UT 84602*
>
>
> 

-- 
Giacomo Fiorin
Associate Professor of Research, Temple University, Philadelphia, PA
Contractor, National Institutes of Health, Bethesda, MD
http://goo.gl/Q3TBQU
https://github.com/giacomofiorin