[gmx-users] Sampling a weak ligand

[Raphaël Robidas]

Hello all,

I am running free energy perturbation calculations to determine the
absolute affinity of a weak ligand. To prevent dissociation and increase
sampling, the first few lambda states introduce a harmonic restraint via
the intermolecular interactions feature. The problem is that my ligand
dissociates in the first state, which has no restraint at all. Is there a
technique to still get an accurate value? I plan on running a longer
simulation for the first state in order to sample more the bound state, but
I hope that there is a smarter way!

Thanks and happy holidays!