Hii,
I want to know if it is a good choice to do model refinement with online server like 3D refine after model generation instead of Molecular dynamics?
I have run the molecule simulations up to 10ns for my structure also but when I was docking the ligand after simulations ithe interactions were totally different?
So, I decided to do the refinement with 3D refine and after docking ligand interactions are somewhat similiar so I want to know if it is okay to use web server for refinement.
Thanks!
One question: What do you mean you mean by "I have run the molecule simulations up to 10ns for my structure also but when I was docking the ligand after simulations ithe interactions were totally different?" ????
This is the workflow we generally use:
1. Docking with ligand
2. Simulation of the complex (protein + ligand)
We don't generally dock the ligand after simulation. I mean you can if you want to with the native protein and not with the simulated protein. Of course you will observe different docking results with the simulated protein because the protein is not in the native state anymore.
Hii Rajesh Pal , Thank you for replying,
What I mean that I generated the model using homology modelling and wanted to do further refinment of my generated model using molecular simulations before docking.
And also I did simualtions for the reference structure which I get from PDB to compare and the results were same as before. So I wanted to know why it was is it because of simulations time or something else?
I think you are mixing up concepts here, we don't perform refinement using molecular simulations.
Nancy Singh : 1) You generate a 3D model of a protein whose structure is not available in PDB
2) You check the quality of the model using ProSA (Z score), QMEAN DisCO, PROCHECK (Secondary structure) etc.
3) You refine the model generated using 3D Refine/ Refine 2, if required you can do additional loop refinement as well
4) Recheck the quality of the protein again to find optimal structural quality of the protein using the above mentioned softwares
5) You use the best model of your protein based on the refinement and final scores for docking with your ligands first
6) Then you perform simulation of the top protein-ligand complexes (based on negative binding energy)
P.S. Don't forget to energy minimize the the protein and ligands before the docking procedure.
Debanjan Kundu Thank you this make it more clear. Actually I have followed all these steps which you mentioned only thing I did the protein simulations before docking and then performed the docking.
Agree with Rajesh Pal. What does it mean- "refinement using molecular simulations"?
Mahbubul Himel Rajesh Pal Nancy might be referring to the fact that protein molecules can be minimised/refined using YASARA, Galaxy Refine or other servers before performing MD simulations. Also, YASARA (and many other minimisation servers) does employ MD simulations to achieve the minimised state of protein molecules. YASARA performs MD simulations (in an implicit solvent and using YASARA2 ff) until the Fmax reaches 0.05 kJ/mol/atom.
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