Here I compare two sets of simulations:
- short simulations: 100 ps for solution (10 fs coordinates sampling time), 10 ps for solvent (100 fs sampling), 10 ns for solute (100 fs sampling) number of insertions for each solvent configuration: 1000 - overall, the same setup as in Karino et al.
- long simulations: 5 ns for solution (200 fs sampling), 5 ns for solvent (20 ps sampling [in fact it is 200 fs but i use skpcnf = 100 ermod option]), 10 ns for solute (100 fs sampling) number of insertions for each solvent configuration: 1000
The slvfe output (including the Long-Range LJ correction), error is 2*sigma here:
Ala (methane)
2.4583 +/- 0.0101 (long simulations)
2.3768 +/- 0.0625 (short simulations)
1.9 +/- 0.02 (Karino et al.)
As (acetamide)
-8.7989 +/- 0.0327 (long simulations)
-8.7276 +/- 0.2463 (short simulations)
-9.2 +/- 0.02 (Karino et al.)
Ile (n-butane)
3.7025 +/- 0.0176 (long simulations)
4.0883 +/- 0.0953 (short simulations)
3.0 +/- 0.02 (Karino et al.)
It seems that the result is sensitive to the simulation length.
I checked the simulations of methane in vacuum and it looks OK to me: no much of distortion from the initial structure. I think that the strange behavior in you case can be explained by the lack of energy exchange between atoms in the molecule (in the solution there is always a heat exchange between the solute and the neighboring solvent molecules, but in vacuum it is not the case). I think, that the Nose-Hoover thermostat (which was used in Karino et al.) in this case might lead to instability. Now there is a warning in Gromacs that for such simulation it is better to use a stochastic integrator ("sd" in gromacs notation, Langevin thermostat). The same story with the BAR simulations, when I used Nose-Hoover thermostat for nearly-decoupled state simulations I occasionally got LINCS crashes.
I use sd integrator + thermostat with tau-t = 2 ps for all simulations.
I also use 4 digit precision for my XTC files, maybe this could be source of differences? I will try to check it.
Moreover, I found the output of the "slvfe" to be quite strange. For long simulations I have identical cumulative solvation energy and solvation free energy average values for all blocks, BUT cumulative errors are NOT zero (which I would expect in this case)? Could it be an indication that something is going wrong?
Here is the example output of "slvfe":
bash-3.2$ cat ../ala/ermod/slvfe.log
Number of the 1-th solvent = 896
Self-energy of the solute = -0.0001 kcal/mol
cumulative average & 95% error for solvation energy
1 -2.8941
2 -2.8941 0.0177
3 -2.8941 0.0180
4 -2.8941 0.0129
5 -2.8941 0.0171
6 -2.8941 0.0180
7 -2.8941 0.0154
8 -2.8941 0.0135
9 -2.8941 0.0120
10 -2.8941 0.0121
group solvation free energy error difference
1 2.82589 0.01104 -0.00087
2 2.81819 0.01048 -0.00857
3 2.82676 0.01009 0.00000
4 2.84026 0.01006 0.01350
5 2.81486 0.01027 -0.01190
6 2.87281 0.00991 0.04605
7 2.80653 0.01112 -0.02023
8 2.79893 0.01034 -0.02783
9 2.92415 0.00887 0.09739
10 2.82960 0.01027 0.00284
12 2.97310 0.00809 0.14634
14 2.77163 0.01131 -0.05513
16 2.93561 0.00993 0.10885
18 3.06915 0.01093 0.24239
20 3.01108 0.00882 0.18432
group Estimated free energy (kcal/mol)
1 2.8440 2.8038 2.8048 2.8313 2.8601
2.8161 2.8210 2.8156 2.8296 2.8326
2 2.8348 2.7961 2.8006 2.8206 2.8521
2.8100 2.8121 2.8090 2.8235 2.8231
3 2.8443 2.8063 2.8077 2.8277 2.8583
2.8183 2.8217 2.8195 2.8333 2.8306
4 2.8579 2.8200 2.8248 2.8410 2.8733
2.8299 2.8374 2.8312 2.8422 2.8448
5 2.8283 2.7931 2.7967 2.8143 2.8497
2.8066 2.8134 2.8076 2.8176 2.8213
6 2.8880 2.8551 2.8559 2.8700 2.9066
2.8628 2.8717 2.8658 2.8707 2.8815
7 2.8227 2.7848 2.7862 2.8044 2.8436
2.7979 2.8056 2.7968 2.8078 2.8155
8 2.8167 2.7776 2.7837 2.8010 2.8311
2.7860 2.7956 2.7885 2.8026 2.8065
9 2.9356 2.9095 2.9071 2.9173 2.9533
2.9157 2.9295 2.9210 2.9185 2.9340
10 2.8476 2.8072 2.8158 2.8327 2.8603
2.8131 2.8274 2.8220 2.8321 2.8379
12 2.9857 2.9573 2.9608 2.9729 2.9978
2.9603 2.9763 2.9688 2.9686 2.9825
14 2.7916 2.7490 2.7550 2.7751 2.8057
2.7566 2.7665 2.7593 2.7762 2.7813
16 2.9474 2.9217 2.9193 2.9269 2.9692
2.9248 2.9407 2.9284 2.9287 2.9490
18 3.0753 3.0585 3.0538 3.0487 3.0993
3.0622 3.0860 3.0695 3.0511 3.0870
20 3.0290 2.9913 3.0096 3.0123 3.0297
2.9895 3.0111 3.0045 3.0094 3.0244
cumulative average & 95% error for solvation free energy
1 2.8443
2 2.8443 0.0380
3 2.8443 0.0249
4 2.8443 0.0181
5 2.8443 0.0203
6 2.8443 0.0170
7 2.8443 0.0144
8 2.8443 0.0126
9 2.8443 0.0112
10 2.8443 0.0101