TMD biasing

From: Felipe Merino (felmerino_at_uchile.cl)
Date: Thu May 14 2009 - 06:23:23 CDT

Dear NAMD guys:

I am interested in the conformational change that a protein shows when
its ligand is bound, so i tried with the targeted molecular dynamics
implementation in NAMD. (NAMD 2.7). When i tried the algorithm in the
"traditional way" everything went fine, with the protein going between
the two states in 1 ns of simulation. Then i wanted to try the biasing
pontential in other way. The idea was to divide the pathway in several
windows with different fixed RMSD with the target. Due to the tmd
potential is an harmonic potential i believed that i later could use the
results for a WHAM calculation using the Grossfield's code to obtain the
PMF associated with the transformation. I rememeber that this TMD/WHAM
procedure was tried before using AMBER for some transformation of
nucleic acids with good results. However, when a tried to use a fixed
target RMSD over the simulation in a config like

TMD on
TMDk 400
TMDOutputFreq 10
TMDFile target.pdb
TMDInitialRMSD 4.3
TMDFirstStep 1000000
TMDFinalRMSD 4.3
TMDLastStep 1100000

the biasing was not applied. Nevertheless i tried to modify it to obtain
something at least approximated. The first solution that i imagined, and
probably not the most elegant, was to define the intial and final RMSD
values with some "delta RMSD" to see if that biasing worked then, so
using this protocol

TMD on
TMDk 400
TMDOutputFreq 10
TMDFile target.pdb
TMDInitialRMSD 4.30001
TMDFirstStep 1000000
TMDFinalRMSD 4.39999
TMDLastStep 11000000

the protein goes close to the target value. My question is: Am i missing
something about my first try with the InitialRMSD=FinalRMSD that makes
the bias not to apply or the code just does not that trick? Anyway, i
think that my second choice could give me some approximation to the PMF
in the end.

Best regards

Felipe Merino, MSc (c)

Laboratorio de Bioquímica y Biología Molecular
Facultad de Ciencias
Universidad de Chile

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