Hi all! I encountered an error in my relative free energy calculations and do not know how to fix it. Molecules for which I want to carry out calculations contain a carboxyl group. To validate the protocol, I tried to run the fep-calculations of symmetric molecules for which the change in free energy will be zero. During validation, I was faced with the fact that the convergence error for charged ligands greatly exceeds that for neutral ones. For example, for the case of m-methyl benzoic acid [O-]C(= O)c1cc(C)ccc1: Mutation (-CH3 + H) for one meta position (-H + CH3) for another meta position relative to the carboxyl group.
Ionized acid (solvent leg, 5 ns): point 0 - 1, DG 28.74 +/- 0.02 point 1 - 2, DG 53.79 +/- 0.41 point 2 - 3, DG 27.76 +/- 2.45 point 3 - 4, DG 18.51 +/- 2.95 point 4 - 5, DG 8.80 +/- 0.79 point 5 - 6, DG 4.04 +/- 0.07 point 6 - 7, DG -0.06 +/- 0.04 point 7 - 8, DG -2.62 +/- 0.33 point 8 - 9, DG -8.95 +/- 0.27 point 9 - 10, DG -23.89 +/- 1.61 point 10 - 11, DG -29.32 +/- 1.29 point 11 - 12, DG -54.15 +/- 0.08 point 12 - 13, DG -28.79 +/- 0.03 total 0 - 13, DG -6.12 +/- 3.19 Unionized acid (solvent leg, 5 ns): point 0 - 1, DG 0.08 +/- 0.01 point 1 - 2, DG -6.88 +/- 0.10 point 2 - 3, DG -14.69 +/- 0.05 point 3 - 4, DG -21.07 +/- 0.03 point 4 - 5, DG -13.21 +/- 0.02 point 5 - 6, DG -7.46 +/- 0.02 point 6 - 7, DG -0.09 +/- 0.03 point 7 - 8, DG 7.37 +/- 0.02 point 8 - 9, DG 13.24 +/- 0.03 point 9 - 10, DG 21.15 +/- 0.06 point 10 - 11, DG 14.72 +/- 0.03 point 11 - 12, DG 6.98 +/- 0.07 point 12 - 13, DG -0.05 +/- 0.01 total 0 - 13, DG 0.09 +/- 0.22 For a neutral molecule containing a charged carboxyl and amino groups ([O-]C(=O)c1cc(C)c([NH3+])cc1) the error is small: point 0 - 1, DG -4.65 +/- 0.01 point 1 - 2, DG -19.95 +/- 0.04 point 2 - 3, DG -28.67 +/- 0.13 point 3 - 4, DG -57.84 +/- 0.19 point 4 - 5, DG -44.18 +/- 0.08 point 5 - 6, DG -26.84 +/- 0.05 point 6 - 7, DG 0.10 +/- 0.20 point 7 - 8, DG 26.92 +/- 0.06 point 8 - 9, DG 44.28 +/- 0.13 point 9 - 10, DG 57.79 +/- 0.13 point 10 - 11, DG 28.68 +/- 0.09 point 11 - 12, DG 19.98 +/- 0.12 point 12 - 13, DG 4.66 +/- 0.03 total 0 - 13, DG 0.28 +/- 0.21 Adding Na and Cl ions to ([O-]C(=O)c1cc(C)c([NH3+])cc1) does not cause an increase in error. point 0 - 1, DG -4.61 +/- 0.01 point 1 - 2, DG -19.96 +/- 0.07 point 2 - 3, DG -28.68 +/- 0.04 point 3 - 4, DG -57.67 +/- 0.04 point 4 - 5, DG -44.24 +/- 0.01 point 5 - 6, DG -26.91 +/- 0.04 point 6 - 7, DG 0.03 +/- 0.03 point 7 - 8, DG 26.89 +/- 0.03 point 8 - 9, DG 44.20 +/- 0.08 point 9 - 10, DG 57.75 +/- 0.09 point 10 - 11, DG 28.65 +/- 0.06 point 11 - 12, DG 20.02 +/- 0.05 point 12 - 13, DG 4.67 +/- 0.01 total 0 - 13, DG 0.12 +/- 0.18 FEP-part of *.mdp: free-energy = yes sc-power = 1 sc-alpha = 0.5 sc-coul = yes fep-lambdas = 0.0 0.01 0.05 0.1 0.2 0.3 0.4 0.6 0.7 0.8 0.9 0.95 0.99 1.0 coul-lambdas = 0.0 0.01 0.05 0.1 0.2 0.3 0.4 0.6 0.7 0.8 0.9 0.95 0.99 1.0 vdw-lambdas = 0.0 0.01 0.05 0.1 0.2 0.3 0.4 0.6 0.7 0.8 0.9 0.95 0.99 1.0 What is the reason of such error and how I can fix it? mdp, itp, gro, xvg files by link - https://drive.google.com/open?id=1MiepOQb2QAZ9rclpY13owCnl8QWcTHnf Ready to provide any additional information. Thank you, Shekhovtsov Artem -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
