Dear all, I am calculating the mutation free energies using TI method for a small globulin protein which contains about 40 residues. I meet convergence problems in the FE calculations: (1) when simulations start with different velocities for the some lambda points, the variance of dGdlamba is big and comparable with ddG (several kJ/mol). That makes the calculation not well reproducible. (2) the error estimates using block averaging method is also large. The error is comparable calculated ddG ( ~4 kJ/mol ). Thus the results seems not very reliable.
By reading, I understand this is due to inefficient sampling for mutations in proteins. I attach one of my dgdl plots for LJ mutation(W->A) step (charges for mutated atoms are removed in previous step). I try to increase the dgdl data collection time to 2ns, which is relative long compared to time used in protein mutation in the references. But the large variance in lambda=0.7, 0.8, 0.9 seems not get improved. The error is also not well reduced. The follwing are the dG results and error in kJ/mol. dG(500ps) = 1.01 error = 3.92 dG(500ps_run1) = -0.40 error = 3.83 dG(1ns) = 2.21 error = 3.67 dG(2ns) = 2.44 error = 3.22 dG(2ns_run1) = -1.02 error = 2.48 Can anybody give some suggestions on how to improve the convergence and reduce the statistical error? I appreciate anyone with free energy calculation experience can give some advice. Thanks Qiang
<<attachment: dgdl.jpg>>
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