Hi Vinay,

You can validate the docking results with MD simulations, and you can also verify the results with actual experiments such as X-ray crystal structures. Creative Biostructure is an expert in the field of structure determination, and maybe you can ask them for technical support.

All the best.

MD simulations can tell you how stable your docked complex is, i.e. whether the ligand has docked within the binding site in a stable conformation and forms adequate molecular interactions which sustain over a significant period of time. But to validate your docking run, you should ideally dock a known natural substrate/inhibitor/agonist/binder of your target's binding site along with your query ligand(s). If the binding energy or IC50 for the known binders is also known through in vitro studies, even better. This allows you to compare the docking scores/energies and binding poses with a reference/control.

Pujan Sasmal Sir, thanks for the advice. Can you please help me out with a detailed protocol for the overlapping of crystal and redocked, and calculating the RMSD value? Thanks in advance!

Dear Vinay Mohan Kandpal . See the following useful RG link: Article Validation of Molecular Docking Programs for Virtual Screeni...

Kindly see also the following useful RG links: Article Molecular docking, validation, dynamics simulations, and pha...

https://www.ccdc.cam.ac.uk/researchandconsultancy/ccdcresearch/researchthemes/methodsandvalidationinmoleculardocking/

Also check please the following useful RG link: Article Validation of Molecular Docking Calculations Involving FGF-1 and FGF-2

The following links are also very useful: https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.204.6418&rep=rep1&type=pdf

https://kuhnlab.natsci.msu.edu/publication_papers/pdf/Zavodszky_Kuhn_JMedChem_2005.pdf

Hello Vinay Mohan Kandpal

1st you have to do the re-docking of the co-crystal with the protein and you can superimpose those complexes in Chimera to see the overlapping of the ligands.

Regards

After docking, perform the simulations to using GROMACS or some other package to check the stability of the protein ligand interactions.

Before studying any ligand binding profile to and target, you must first establish and validate a docking procedure. To do so, if your target has a co-crystalized ligand in its binding pocket, you can extract and re-dock in the same binding pocket. Then, by taking the initial structure as reference, you can superimpose the docked structure and compute the RMSD. If this value is lower than 2 Å for almost the 10 or more conformer with highest docking score, you can consider your docking procedure good. Further, you can also perform MD simulations to investigate the stability of the interactions between the re-dock complex. By looking the RMSD and visualizing the structure from the production stage, you can be further convince for the accuracy of your docking procedure (this verification is not an obligation, the first one is enough). After validating your docking procedure, you can use it to dock your compounds and perform post-docking process such as free energy perturbations analysis, MM-PBSA/GBSA, MD simulations analyses an so on. Several popular softwares for these studies are Schrodinger, MOE, AMBER, GROMACS, Chimera an so on.

Incase your protein has no co-crystal structure. What are the ways to validate the docking scores?. Thank You