Hello,
I am running TI to calculate absolute binding free energy of a ligand to
a enzyme,
and hydration free energy of Mg2+. In both cases, I have the same
problem at the window
of lambda 0.0 of vdW transformation:
dummy in water -> a particle in water (LJ126), for Mg2+
dummy atoms in protein/water -> ligand in protein/water (LJ126), for
ligand binding
Here is the input:
TI simulation
&cntrl
imin = 0, nstlim = 2500000, irest = 1, ntx = 5, dt = 0.002,
ntt = 3, temp0 = 300.0, gamma_ln = 2.0, ig = -1,
ntc = 2, ntf = 1,
ntb = 2, cut = 10.0 ,
ntp = 1, pres0 = 1.0, taup = 2.0, barostat = 2 ,
ioutfm = 1, iwrap = 1, nmropt = 0 ,
ntwe = 50, ntwx = 25000, ntpr = 50, ntwr = 50000,
icfe = 1, clambda = 0.000, scalpha = 0.5, scbeta = 12.0,
logdvdl = 50, ifmbar = 1, mbar_states = 25,
mbar_lambda =
0.000,0.001,0.005,0.050,0.100,0.150,0.200,0.250,0.300,0.350,0.400,0.450,0.500,0.550,0.600,0.650,0.700,0.750,0.800,0.850,0.900,0.950,0.995,0.999,1.000
,
ifsc=1, scmask1='', scmask2=':599', timask1= '' , timask2=':599',
crgmask=':599' ,
/
:599 could be the ligand or the Mg2+.
In the output I found this:
MBAR Energy analysis:
Energy at 0.0000 = -347175.261389
Energy at 0.0010 = -347175.277294
Energy at 0.0050 = -347175.339599
Energy at 0.0500 = -347175.883645
Energy at 0.1000 = -347176.092259
Energy at 0.1500 = -347175.774626
Energy at 0.2000 = -347174.781819
Energy at 0.2500 = -347172.913973
Energy at 0.3000 = -347169.898353
Energy at 0.3500 = -347165.355646
Energy at 0.4000 = -347158.746665
Energy at 0.4500 = -347149.285216
Energy at 0.5000 = -347135.790332
Energy at 0.5500 = -347116.423987
Energy at 0.6000 = -347088.200343
Energy at 0.6500 = -347046.005721
Energy at 0.7000 = -346980.476944
Energy at 0.7500 = -346872.902025
Energy at 0.8000 = -346681.120206
Energy at 0.8500 = -346291.827917
Energy at 0.9000 = -345297.965604
Energy at 0.9500 = -341015.400345
Energy at 0.9950 = -89656.787916
Energy at 0.9990 = 3442279.987340
Energy at 1.0000 = ****************
The energy at window 1.0 is extremely high. This also happened in some
windows of my calculation of Mg2+ hydration free energy using one-step
transformation from dummy in water to Mg2+ in water.
I tried to turn off the MBAR analysis by setting ifmbar=0, it did not
change the results though I did not see the large energy number from
MBAR energy analysis.
I tried to run the tutorial, ligand transformation, but I don't have the
problem.
https://ambermd.org/tutorials/advanced/tutorial9/index.html
I don't have the issue with sander, either. I tried some reference
calculations.
I searched the mailing list, there were also some people having the same
problem, but I did not see a solution to it. Any suggestions? Thanks
very much!
All the best,
Qinghua
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Received on Thu Nov 04 2021 - 08:30:03 PDT
