Binding energy calculation for multiple ligands in a complex

[Gustavo Avelar Molina]

Dear gmx_MMPBSA users,

My system of interest is a homotetrameric protein in which each subunit can bind a ligand. I seem to have successfully calculated the binding energy of one ligand with the tetramer using gmx_MMPBSA. In this case, the ligand interacts mainly with one of the monomers. I have two questions about that:

1. Suppose I have a trajectory in which each subunit is bound to a ligand. Is it theoretically possible and or/appropriate to calculate the binding energy (e.g., GB + IE) for each ligand? I suppose it would be computationally convenient to do so because then I could increase the number of replicates and thus save on computational resources.

2. If the answer to 1 is positive, then how can I account for the presence of the other ligands when iteratively calculating the binding energy of each ligand? Can I simply use an index file with a receptor group containing the tetramer and the other three ligands?

3. Still if 1 is positive, can gmx_MMPBSA handle this specific problem automatically or at least automate the work at any step?

Thank you in advance.

Best regards,

Gustavo

[gmx_MMPBSA]

The way to do this is to consider one ligand at a time and consider the rest (homotetramer + 3 ligands as receptors) as you suggested. It will increase the number of replicates as you pointed out although you will have to run 4 calculations independently. The process could be easily automated using Python or another scripting language. You just create the corresponding groups in the index file and then run the calculations with the groups of interest

hope this helps!

[Gustavo Avelar Molina]

Thanks a lot for the input!

Best regards,

Gustavo