VMD-L Mailing List

From: McGuire, Kelly (mcg05004_at_byui.edu)
Date: Fri May 25 2018 - 10:30:48 CDT

Thank you for the response! I always worried about biasing with deleting water molecules at each new position when I was shown umbrella sampling for the first time. I would like to avoid that if possible.

Kelly L. McGuire

PhD Scholar

Department of Physiology and Developmental Biology

Brigham Young University

LSB 3050

Provo, UT 84602

________________________________
From: Giacomo Fiorin <giacomo.fiorin_at_gmail.com>
Sent: Friday, May 25, 2018 7:09:32 AM
To: McGuire, Kelly
Cc: VMD Mailing LIst
Subject: Re: vmd-l: ABF Calculations Question 1

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<mailto: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