[gmx-users] free energy calculations using MBAR and gromacs

[Gurpreet Singh]

Hi,

 I am trying to calculate free energy of a system that involves
disappearance of LJ particle at lambda=1 in explicit solvent. I ran the
simulation at 20 different lambda points ranging from 0 to 1, using soft
core potential. In order to use MBAR method (python implementation from
Michael shirts ), I have to rerun the simulations, in order to get
potential energies for each configuration at every lambda point. Now,
here i get into trouble. If i evaluate the trajectories generated at
lambda = 1 (particle completely decoupled) using the potential function
at lambda = 0, i get very large energy values, which quite likely are
responsible for MBAR's failure to converge . The program works well if i
calculate free energy to/from an intermediate. ie lambda 0 -> 0.5 and
0.5->1.0 
As the potential energies for the configurations generated at lambda=1,
evaluated using potential energy function at lambda =0, is expected to
be infinite (due to Van der Waals overlaps between solvent and LJ
particle), Is it even possible to apply MBAR method to such cases,
without splitting the analysis to an intermediate lambda value? Did
anyone ran into similar problems, or am i missing something? 

With Regards,
Gurpreet