Visvaldas Kairys

OK, I sort of get it: when I take NEGATIVE weight values then affinity seems to be exactly equal to the term weights times term values. Weights Terms -1 gauss(o=0,_w=0.8,_c=8) Name gauss(o=0,_w=0.8,_c=8) Affinity: -149.73016 (kcal/mol) Intramolecular energy: -13.71686 Term values, before weighting: 149.73016 The lingering question remains if the term value itself includes the intramolecular ligand energy. I suspect that it doesn't. The funny thing if the weight is positive then the affinity is equal...

I need to modify ligand intramolecular energies (in my case, some ligand intramolecular clashes are only visible in QM but not in FF). Is there a way to extract purely intermolecular interaction in the "score_only" mode? Right now, the term weights times term values plus the reported intramolecular interaction do not add up to the total binding affinity. It seems that the binding affinity equation is quite complicated. Even how intramolecular energy is calculated based on the weights is also shrouded...

Something's still bothering me. Intra-ligand energies are calculated using different rules than P-L (protein-ligand) interactions (e.g. the term weights seems to be gone, etc.), and I am afraid intra-L energy quality is worse than P-L just because P-L terms are so carefully weighted and so much research has been input into it. I am not sure if I make myself clear or if I am correct. (And flex sidechain interaction with small molecule is intra-ligand from the viewpoint of the program if I understand...

Well, in the rigid docking the flex residues are obviously different from flexible docking (zero flex residues vs one), so I the mismatch between scores is understandable. I guess the whole thread could be deleted :) But I will do the "refrozen" sidechain docking anyway because that particular sidechain rotamer im interested in for some ligands in the series somehow is not accessible because it (or rather ligand poses that are modulated by that sidechain rotamer) is higher in energy. That's why the...

I understand and agree with your evaluation of the what's happening. However, I find the mismatch between the flexible and rigid receptor scores (and therefore pose rankings) troubling. I guess from now on I will be freezing the flex sidechains from the minima and re-running the "reconstituted" rigid dockings...

Merry Christmas! I've noticed some possible flaw of flex sidechain code (probably originating in the original Vina code, which I admittedly haven't tested for this). If I do flexible docking using Smina, then afterwards rebuild the receptor with modified flex'ed sidechains, and do a simple rescoring (I used vinardo), the rescored scores deviate quite significantly and seemingly randomly (by up to ±2 kcal/mol) from the original flexible docking scores. I wonder if this could be one of the reasons...

Sorry this is a rhetorical comment. My student just now was doing docking with the recently updated "mainstream" AutoDock, and at exhaustiveness =100 and vinardo scoring he got variation of about 0.5 kcal/mol for the same ligand/receptor pair with different random seeds. Smina on the other hand gives 0-0.1 kcal/mol variation for the ligands he has tested. So, praise to Smina, and warning regarding the "vanilla" AutoDock (probably needs to be debugged).

Now it seems to work fine. I don't understand why I had so hard time tuning exhaustiveness previously. Maybe it does have to do with the random seeds. When the problem happens again, I will let you know. Sorry for the disturbance...