I am currently busy with my master's research project and I'm trying to calculate the free energy of separation of two cellobiose molecules in ionic liquid, that is, calculate the free energy of separating two molecules from a distance of 35 nm to 215 nm. I have tried steered molecular dynamics with the Jarzynski relation, taking the logarithm of the radial distribution function and various umbrella sampling methods, but none of them seem to give me good FE profiles.
I think my system (1-butyl-3-methylimidaozlium acetate) just isn't going to give good FE profiles, but my supervisor is convinced that it will. I am currently trying thermodynamic cycles out so I hope that works.
So, my question is, what other methods for calculating the FE of separating the cellobiose molecules are there? And can you provide tutorials for me for those? I am aware of slow growth, ABMD, NFE, metadynamics, etc. but either these do not have any useful tutorials or don't work in the AMBER force field.
I have been struggling with this for more than two months now and my supervisor does not want me to stop my analysis. What other method can I use? Is there other computational methods available for determining the interaction between two systems?
Thank you in advance.