[gmx-users] free energy calculations of methane in water computed by GMX ver 4.5.7 and ver 4.6.2

[Dwey]

Hi gmx-users,

     I almost  reproduced  free energy calculations of methane in water on
Justin's website. First of all, I am able to follow the workflow of
computing solvation free energy  for several times with Gromacs version
4.5.7 and version 4.6.2 installed in two identical Linux boxes.

However.  the output results of GMX ver 4.5.7 and ver 4.6.2 show different
values of dG

##################################
GMX Ver. 4.5.7:

lambda  0.000 -  0.050,   DG  0.05 +/-  0.00
lambda  0.050 -  0.100,   DG  0.01 +/-  0.00
lambda  0.100 -  0.150,   DG -0.03 +/-  0.01
lambda  0.150 -  0.200,   DG -0.08 +/-  0.00
lambda  0.200 -  0.250,   DG -0.15 +/-  0.00
lambda  0.250 -  0.300,   DG -0.21 +/-  0.01
lambda  0.300 -  0.350,   DG -0.28 +/-  0.00
lambda  0.350 -  0.400,   DG -0.38 +/-  0.00
lambda  0.400 -  0.450,   DG -0.50 +/-  0.01
lambda  0.450 -  0.500,   DG -0.66 +/-  0.01
lambda  0.500 -  0.550,   DG -0.90 +/-  0.01
lambda  0.550 -  0.600,   DG -1.21 +/-  0.01
lambda  0.600 -  0.650,   DG -1.37 +/-  0.01
lambda  0.650 -  0.700,   DG -1.25 +/-  0.01
lambda  0.700 -  0.750,   DG -0.96 +/-  0.00
lambda  0.750 -  0.800,   DG -0.62 +/-  0.00
lambda  0.800 -  0.850,   DG -0.31 +/-  0.00
lambda  0.850 -  0.900,   DG -0.03 +/-  0.00
lambda  0.900 -  0.950,   DG  0.20 +/-  0.00
lambda  0.950 -  1.000,   DG  0.38 +/-  0.00

total   0.000 -  1.000,   DG -8.31 +/-  0.04

##################################

GMX ver. 4.6.2 ver

point  0.000 -  0.050,   DG  0.00 +/-  0.00
point  0.050 -  0.100,   DG -0.03 +/-  0.00
point  0.100 -  0.150,   DG -0.08 +/-  0.00
point  0.150 -  0.200,   DG -0.14 +/-  0.00
point  0.200 -  0.250,   DG -0.20 +/-  0.00
point  0.250 -  0.300,   DG -0.27 +/-  0.00
point  0.300 -  0.350,   DG -0.34 +/-  0.00
point  0.350 -  0.400,   DG -0.43 +/-  0.01
point  0.400 -  0.450,   DG -0.54 +/-  0.01
point  0.450 -  0.500,   DG -0.71 +/-  0.01
point  0.500 -  0.550,   DG -0.94 +/-  0.01
point  0.550 -  0.600,   DG -1.24 +/-  0.02
point  0.600 -  0.650,   DG -1.39 +/-  0.02
point  0.650 -  0.700,   DG -1.28 +/-  0.01
point  0.700 -  0.750,   DG -1.00 +/-  0.00
point  0.750 -  0.800,   DG -0.67 +/-  0.00
point  0.800 -  0.850,   DG -0.36 +/-  0.00
point  0.850 -  0.900,   DG -0.09 +/-  0.00
point  0.900 -  0.950,   DG  0.14 +/-  0.00
point  0.950 -  1.000,   DG  0.33 +/-  0.00

total  0.000 -  1.000,   DG -9.23 +/-  0.03

##################################


The value of DG (= -9.23 kJ mol -1)  by GMX ver 4.6.2 is very close to that
by Justin or Shirts et.al of 2.24 kcal mol-1  (~ -9.36 kJ mol -1), while
that of GMX ver 4.5.7 ( =-8.31 kJ mol-1) is far away.

I wonder if someone has similar experience to explain the inconsistency
between the outputs from ver 4.5.7 (~-8.31 kJmol-1)  and ver 4.6.2 (-9.23
kJmol-1 ), despite  the values of dG computed by others.


Second,  the reason why I almost reproduced dG  but not completely is
 because I removed the step of  L- BFGS minimization.  I was not able to
pass this step  for both GMX versions.  Here shows the warning.

++++++++++++++++++++++++++++

Fatal error:
The combination of constraints and L-BFGS minimization is not implemented.
Either do not use constraints, or use another minimizer (e.g. steepest
descent).

++++++++++++++++++++++++++++

L-BFGS mdp file can be found  at
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/Files/em_l-bfgs.mdp

Again, I appreciate advice or  a hint.

Thanks,

Dwey