Dear GMX users Hi. I'm calculating some small organic molecule's desolvation free energy. Recently i got this error from BAR calculation. Please anyone explain what's wrong in here?
First: WARNING: Using the derivative data (dH/dlambda) to extrapolate delta H values. This will only work if the Hamiltonian is linear in lambda. and then Second: WARNING: Some of these results violate the Second Law of Thermodynamics: This is can be the result of severe undersampling, or (more likely) there is something wrong with the simulations. I have two MD simulation steps. For example desolvation free energy of chloroform and methanol: The final result from MD1 something like this: total 0.000 - 1.000, DG 7.72 +/- 0.05 The final result from MD2 something like this: total 0.000 - 1.000, DG 3.96 +/- 0.06 Total Gibbs energy of desolvation 11.7 +/- 0.1 kJ/mol (including with these two warnings) Something wrong in MD? MD1.mdp ;Run control integrator = sd ; Langevin dynamics tinit = 0 dt = 0.002 nsteps = 1000000 ; 2 ns nstcomm = 100 ; Output control nstxout = 500 nstvout = 500 nstfout = 0 nstlog = 500 nstenergy = 500 nstxtcout = 0 xtc-precision = 1000 ; Neighborsearching and short-range nonbonded interactions nstlist = 10 ns_type = grid pbc = xyz rlist = 1.0 ; Electrostatics coulombtype = PME rcoulomb = 1.0 ; van der Waals vdw-type = switch rvdw-switch = 0.8 rvdw = 0.9 ; Apply long range dispersion corrections for Energy and Pressure DispCorr = EnerPres ; Spacing for the PME/PPPM FFT grid fourierspacing = 0.12 ; EWALD/PME/PPPM parameters pme_order = 6 ewald_rtol = 1e-06 epsilon_surface = 0 optimize_fft = no ; Temperature coupling ; tcoupl is implicitly handled by the sd integrator tc_grps = system tau_t = 0.2 ref_t = 300 ; Pressure coupling is on for NPT Pcoupl = Parrinello-Rahman tau_p = 5 compressibility = 4.5e-05 ref_p = 1.0 ; Free energy control stuff free_energy = yes init_lambda = 0.0 delta_lambda = 0 foreign_lambda = 0.05 sc-alpha = 0.5 sc-power = 1.0 sc-sigma = 0.3 couple-lambda0 = vdw-q ; only van der Waals interactions couple-lambda1 = vdw ; turn off everything, in this case only vdW couple-intramol = no nstdhdl = 10 ; Do not generate velocities gen_vel = no ; options for bonds constraints = all-bonds ; ; Type of constraint algorithm constraint-algorithm = lincs ; Constrain the starting configuration ; since we are continuing from NPT continuation = yes ; Highest order in the expansion of the constraint coupling matrix lincs-order = 12 MD2.mdp ;Run control integrator = sd ; Langevin dynamics tinit = 0 dt = 0.002 nsteps = 1000000 ; 2 ns nstcomm = 100 ; Output control nstxout = 500 nstvout = 500 nstfout = 0 nstlog = 500 nstenergy = 500 nstxtcout = 0 xtc-precision = 1000 ; Neighborsearching and short-range nonbonded interactions nstlist = 10 ns_type = grid pbc = xyz rlist = 1.0 ; Electrostatics coulombtype = PME rcoulomb = 1.0 ; van der Waals vdw-type = switch rvdw-switch = 0.8 rvdw = 0.9 ; Apply long range dispersion corrections for Energy and Pressure DispCorr = EnerPres ; Spacing for the PME/PPPM FFT grid fourierspacing = 0.12 ; EWALD/PME/PPPM parameters pme_order = 6 ewald_rtol = 1e-06 epsilon_surface = 0 optimize_fft = no ; Temperature coupling ; tcoupl is implicitly handled by the sd integrator tc_grps = system tau_t = 0.2 ref_t = 300 ; Pressure coupling is on for NPT Pcoupl = Parrinello-Rahman tau_p = 5 compressibility = 4.5e-05 ref_p = 1.0 ; Free energy control stuff free_energy = yes init_lambda = 0.0 delta_lambda = 0 foreign_lambda = 0.05 sc-alpha = 0.5 sc-power = 1.0 sc-sigma = 0.3 couple-lambda0 = vdw ; only van der Waals interactions couple-lambda1 = none ; turn off everything, in this case only vdW couple-intramol = no nstdhdl = 10 ; Do not generate velocities gen_vel = no ; options for bonds constraints = all-bonds ; ; Type of constraint algorithm constraint-algorithm = lincs ; Constrain the starting configuration ; since we are continuing from NPT continuation = yes ; Highest order in the expansion of the constraint coupling matrix lincs-order = 12 Thank you so much. Khatnaa -- gmx-users mailing list [email protected] http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to [email protected]. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
