I am practicing Molecular Docking using PyRx software. I tried to confirm whether my docking is appropriate or not by using available crystal structure of a CDK2-dinaciclib (enzyme-inhibitor complex) in the PDB database. After preparing my protein and ligand separately, i tried the docking. I found certain poses but none of them match with the binding mode described in the reported crystal structure. My questions are :-
1) Is it possible to achieve the same binding mode in PyRx Vs PDB crystal structure
2) In my docking out put, why is the inhibitor/dinaciclib binding at different binding site (too far from the proposed conventional binding site i.e hinge region of the same kinase). My compounds are analogues of dinaciclib or similar drugs which are expected to dock in the same region of the kinase)
3) Is it inappropriate not to select an active site of the the kinase/CDK2 during docking using PyRx. If i have to select an active site to get best docking pose, how can i achieve this?
3) Finally, how accurate/acceptable is PyRx Vs alternative docking softwares like Maestro for instance during publication?
Thanks in advance for your responses !!!
Thank you for your interesting question. I am trying to address your questions in following points.
1. Most of the docking softwares (AutoDock 4.2, AutoDock vina) can produce a conformation of a molecule in protein cavity which is very similar to the pdb. It is the validation of docking calculation.
2. In my point of view, your second problem was appeared due to the inappropriate choice of grid box. Set your grid in the region where the ligand was found in pdb file.
3. Proteins have an site to perform it's normal activities. Therefore you need to select.
4. AutoDock 4.2, AutoDock vina (both are free), MOE, Meastro are most accurate and acceptable software in this time.
Nayim Sepay Thank you Nayim for your nice answer. In fact, I propose my compounds would bind a certain region in the kinase which I can select with the grid box. But, I am concerned that I will miss the chance if my compound has a potential (theoretical though) for docking in a region other than the usual binding site. Based on this I did the docking exercise by simply selecting the whole protein into the grid box.
I will certainly apply your recommendation. Thanks again!
Pujan Sasmal
Thanks for your suggestion. I found an interesting explanation in a youtube video (Webinar - Introduction to Molecular Docking, https://www.youtube.com/watch?v=NLrjHq89fYM)at exactly 1:22:02.- Badges
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