FEP Calculations Protein-Protein Complex

User discussions
1

GROMACS version:2024.1
GROMACS modification: Yes/No

Here, post your question

Is it a good approach if we rename two protein chains, A & B, to common chain C without changing structural integrity?
Because while doing FEP calculation, couple-moltype takes only combine protein. It is not working as " copule-moltype = Protein_Chain_A Protein_Chain_B

2

Indeed, couple-moltype only takes one molecule type. However, you can work around that by modifying the B state parameters in your topology.

But beware, free energy perturbations of a whole protein is usually not a good idea. Firstly, it’s very slow. Secondly, you would need to sample very long for the simulation to converge.

3

Thank you. So, what could be a good idea to calculate bindin energy? Can MMPBSA be another option in GROMACS?

4

Pulling the two proteins apart using, e.g., umbrella sampling or AWH could work. But even then you might find that it is challenging calculating the binding free energy of two proteins. I don’t know how well MMPBSA would work - I haven’t tried it.