Dear all,<br> <br>I am calculating the mutation free energies using TI method for a small globulin protein which contains about 40 residues.<br>I meet convergence problems in the FE calculations:<br>(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. <br>
(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.<br> <br>By reading, I understand this is due to inefficient sampling for mutations in proteins. <br>
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.<br>
The follwing are the dG results and error in kJ/mol.<br>dG(500ps) = 1.01 error = 3.92 <br>dG(500ps_run1) = -0.40 error = 3.83 <br>dG(1ns) = 2.21 error = 3.67<br>dG(2ns) = 2.44 error = 3.22<br>
dG(2ns_run1) = -1.02 error = 2.48<br> <br> <br> <br>Can anybody give some suggestions on how to improve the convergence and reduce the statistical error?<br> <br>I appreciate anyone with free energy calculation experience can give some advice.<br>
<br> <br> <br>Thanks<br> <br>Qiang