I am working with Short chain Alcohol dehydrogenase(R-ADH) for converting ketones to alcohols. The reaction mechanism is that the enzyme accepts the ligand, such that its S-face faces towards the co-factor (NADP/NADPH/NADH) with enzyme.For docking the ligand(Acetophenone) I am using autodock4.
With autodock results I get both R and S-face facing towards cofactor,with slight differences in energy(-3.98(R) and -3.08(S)).
My query is that how should I differentiate something like this if I am not aware of the mechanism. Which one I should consider correct.
Another query I have is related to the binding energy values, the values I got(-3.98 and -3.08) are these acceptable or too high for the stable complex.
Thank you
Hello Aditi
I an not sure with your first question but the second one related to energy I will answer.
In Docking we try to find the best binding between ligand and protein, and it explains with the binding ener. So lower the binding energy better is the binding. So your energy is good.
If you need I can share one paper which published long back with regards the binding energy.
Hi Aditi,
Regarding your second question, its true that lower the binding energy better is the binding but you gotta perform MD simulation to analysis the complex and its stability before concluding anything. HTH.
Regards
binding energy of autodock has 2 kcal/mol of standard error. so you cant account on these two binding energy. you have to use of x-score to rescore the resulting poses.
While it is tough to judge the binding energy values as such, an estimate can be gathered by considering relative values instead of relying on absolute values. You could use a known natural substrate or agonist/antagonist of the protein and dock it with the same parameters, as sort of a control, and then compare your ligand's binding energy with respect to it.
Not sure about the R-S configuration question, but if the mechanism is not known, I guess one has to trust the algorithm's score and go with the ligand showing the most negative binding energy value.
yea sure that would be a great help.
For my first question:
Am getting energies too close for both the correct and incorrect conformations but here in this case I am aware of correct conformation.
If something similar happens where am not aware of the correct conformation.In such situation how can i make out which is correct?
@ Sako Mirzaie : Do you have a reference paper to cite that binding energy of autodock has 2 kcal/mol of standard error. If so, please share. I need to cite it in my publication.
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