How to compute the free energy of translocation of ligand using unbiased MD

User discussions
1

GROMACS version: 5.1.4
GROMACS modification: No
Hello,
I have performed an unbiased MD simulation to examine the translocation of the ligand from position A to position B (Approximately 10 Å movement). Is it possible to use the umbrella sampling technique to calculate free energy using the unbiased reaction coordinates? Is there any other technique to calculate free energy for this unbiased event?

Looking forward to your suggestions.
Thanks in advance,
Jana

2

I don’t understand your question. With unbiased MD you can simply use the distribution along the distance to compute the free-energy, but then you need to sample both states. If unbiased MD does not sample both states, you can used biasing method, such as umbrella sampling or AWH. I don’t understand what you mean with an unbiased reaction coordinate.

3

Hi Hess,
Thank you for your reply. I have carried out conventional NPT MD simulation and observed the ligand translocation. The unbiased reaction coordinates mean the translocation path of the ligand. I have calculated the distance throughout the simulation. Could you please tell me how can I get the distribution with distance and please tell me what distribution you are suggesting? Please kindly let me know. Please provide me a reference, if possible.

Thanking you,
Jana