Hi!!
I am a student doing a Master Program in Pharmaceutical Chemistry and I am
writing to get some advice on understanding the results given by WHAM after
doing an Umbrella Sampling of a dissociation process in a protein (600
residues approx.)-peptide interaction.
To separate these molecules, a force constant of 50kcal/mol/ang2 (the
smallest that can keep the distance reasonably steady) is set, and r1 and
r4 values fixed at -1 and +1 unit of each r2=r3 value for every (5 ns
production) window. The increment of distance separation from window to
window is 0.2 angstroms.
The combination of the MD gives a comprehensive separation movement when
visualized in VMD and umbrella sampling looks nice since the overlap of the
simulated windows looks adequate. It is much more full of dots than the
example of the tutorial.
However, I am having difficulties to understand WHAM results.
When looking at the result.dat (as it is called in the AMBER advanced
tutorial 17) we get the following data.
#Coor Free +/- Prob +/-
7.492857 0.000000 0.000089 0.078953 0.000015
7.678571 0.021163 0.000114 0.076200 0.000018
7.864286 0.048638 0.000050 0.072768 0.000005
8.050000 0.035474 0.000201 0.074392 0.000012
8.235714 0.025529 0.000203 0.075644 0.000032
8.421429 0.074532 0.000235 0.069675 0.000034
8.607143 0.010492 0.000132 0.077576 0.000021
8.792857 0.031564 0.000090 0.074882 0.000009
8.978571 0.138947 0.000127 0.062539 0.000005
9.164286 0.160852 0.000055 0.060283 0.000007
9.350000 0.122887 0.000140 0.064246 0.000019
9.535714 0.063552 0.000138 0.070970 0.000021
9.721429 0.063538 0.000176 0.070971 0.000025
9.907143 0.064124 0.000422 0.070902 0.000016
#Window Free +/-
#0 0.000000 0.000000
#1 0.000000 0.000000
#2 0.000000 0.000000
#3 0.015216 0.000000
#4 0.000000 0.000000
#5 0.000000 0.000000
#6 0.000000 0.000000
#7 0.000000 0.000000
#8 0.010285 0.000000
#9 0.000000 0.000000
#10 0.000000 0.000000
#11 0.000000 0.000000
#12 0.000000 0.000000
#13 0.034936 0.000000
The main problem comes when looking at the Free energy, which is used to
see whether the system has converged or not. In the WHAM manual, it is
mentioned that when this F value is smaller than the specified tolerance
the system has converged. The tolerance value set for these results is
10^-6.
Moreover, when doing MonteCarlo Bootstrap analysis to look for similarities
with the information given in the manual, we get 3 iterations; very
different from the information given in the WHAM manual.
I expected the system to be convergent due to a small increment value,
enough simulation time and good overlapping between windows. However, I
find strange to see these F values. The files present in the amber tutorial
do not show these results ( #Window Free and +/-) and the WHAM manual does
not give information about the example used so we do not have a solid
criterion to understand these results.
I would be really grateful if you could help me understand the meaning of
these results for this system and provide any suggestion to perform a
successful umbrella sampling.
Thanks in advance,
Daniel Fernández
PD: We modified the Perl script for minimization, equilibration and
production steps and our own script reads coordinates from the end of the
last production .rst file window performed; and not from the original
coordinates as shown in the tutorial. I am not sure if this is correct but
we thought that this way the system would be less distorted when reaching
high distance values for separation.
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Received on Sat Apr 13 2019 - 06:30:02 PDT
