Can Vina 1.2.5 be used to screen for synergistically/antagonistically bound multiligand

[Tang-Rich]

Hello,
I am concerned about utilizing Vina 1.2.5 in drug combinations after it enables simultaneous docking of multiple ligands. Now the problem encountered is:
-Ligand A can be docked to α-glucosidase alone to obtain binding energy of A
-Ligand B can also dock to α-glucosidase alone to obtain binding energy of B
-A and B are docked simultaneously to obtain binding energy of A+B
Can a potential synergistic/additive/antagonistic relationship between A and B be tentatively determined based on the numerical difference between (binding energy of A +binding energy of B) and (binding energy of A+B)? How about (binding energy of A+B) / (binding energy of A +binding energy of B) ?

The hypothetical premise is that both A and B can form an optimal docking (binding energy judgment) with a particular site. As ligand A binds more strongly to one site, ligand B is forced to bind to other sites. The semi-flexible docking procedure, on the other hand, makes it impossible to assess the magnitude of the effect of the presence of ligand A on ligand B binding. This effect may be manifested in:
-Robbing of the site.
-Changes in the enzyme microconfiguration causing changes in the properties of the other sites
-ligand interactions, etc.
At present we have summarized in the literature the experimental determination of small molecule combinations with synergistic/antagonistic properties, but have not yet found any valuable pattern. However, if screening could be provided using Vina computer simulations, it would cause a stir in the field of drug design.
Answers are also appreciated on the logic of binding energy assessment in Vina 1.2.5 and how to determine the interrelationships of combinations.

[diogomart]

Hello,

It's already very difficult to predict the affinity of a single ligand. For synergism, the uncertainty in the predictions is probably just too large to get anything useful.

One technical caveat: with two ligands in vina, the number of interacting pairs is larger, so the intermolecular energy will be larger, and we didn't calibrate the INTRAmolecular energy contribution to the score. In other words, we just wanted to make it possible to dock multiple ligands simultaneously, but we don't know if the energy predictions are reasonable.