[gmx-users] Umbrella Sampling Results and Issues
agnivogromacs14 at gmail.com
Mon Nov 24 19:03:16 CET 2014
I am doing an umbrella sampling MD to calculate the binding energy between
a DNA and a protein. I am following Dr. Lemkuls tutorial for the same.
Firstly I put the complex in a rectangular box and used the
AMBER99SB-Parmbsc0 forcefield for the topology generation. Then I used SD
for minimization , 1 ns restrained NVT equilibration ( V-rescale , T = 300
K) , 1 ns restrained NPT equilibration ( Berendsen couplings in both , ref
Press = 1 bar , however achieved average press = 0.4 bar with very low
error , RMSD ) , 500 ps Steered Molecular Dynamics keeping DNA fixed and
pulling Protein ( Using Nose-Hoover thermostat , Parinello - Rahman
I pull for a total of 5 nm.
This is the relevant mdp entry for the SMD
; Pull code
pull = umbrella
pull_geometry = distance ; simple distance increase
pull_dim = N N Y ; Z axis reaction coordinate
pull_start = yes ; define initial COM distance > 0
pull_ngroups = 1 ; applying puling force to protein only
pull_group0 = DNA ; reference fixed group for pulling
pull_group1 = Protein ; the molecule to which pulling force is applied
pull_rate1 = 0.01 ; 0.01 nm per ps = 10 nm per ns
pull_k1 = 1000 ; kJ mol^-1 nm^-2 force constant for pulling
After this I extracted the conf.gro files and using the perl/python scripts
from the tutorial extracted 21 windows (0.2 nm spacing) from the SMD
trajectory for the umbrella sampling. In each window I did a 100 ps short
NPT equilibration restraining only the DNA and then an 1 ns umbrella
sampling simulation restraining the DNA with the following mdp entry :
; Pull code
pull = umbrella
pull_geometry = distance
pull_dim = N N Y
pull_start = yes
pull_ngroups = 1
pull_group0 = DNA
pull_group1 = Protein
pull_init1 = 0
pull_rate1 = 0.0
pull_k1 = 1000 ; kJ mol^-1 nm^-2
pull_nstxout = 100 ; every 0.2 ps
pull_nstfout = 100 ; every 0.2 ps
Then I ran the g_wham tool on the results.
I am attaching the PMF profile and the Histogram for reference :
As observed , the PMF is having 3 steps for particular reaction coordinates
and at those regions the Histogram is also not showing ideal overlapping
This is the ERROR output of g_wham :
WARNING, no data point in bin 26 (z=3.04567) !
You may not get a reasonable profile. Check your histograms!
The error file is also attached :
So, my questions are :
Should I decrease the nm spacing to say 0.1 nm around those particular
reaction coordinates where the "no data point in bin" error is coming ? ?
Should I be going for asymmetric windows
OR , should I simultaneously increase my simulation time for umbrella
sampling to say 5 ns from 1 ns ?
Thanks & Regards
Grad Student, Iowa State University.
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