Hi,

Basically from your query i find out that you are conducting study for mutational characterization. I would suggest you to follow 2nd option because after mutating wild type structure when you simulate it in solvent system it will show you whether there is any break in the structure and also is there any shift in the active site of the protein which would indirectly affect your ligand binding to it. Hope this helps.

Regards

If you could use Molecular Dynamics and willing to go further then I'd suggest using MD itself to find out the effect of mutation rather than using docking tools. Sometimes MD could offer more insight that you can not get from docking result. For example:

http://www.ks.uiuc.edu/Research/influenza/

http://www.ks.uiuc.edu/Research/influenza_res/

Ever heard computational alanine scanning? For example:

http://pubs.acs.org/doi/abs/10.1021/jp054760d

If you're using NAMD, this LIE (Linear Interaction Energy) tutorial could be helpful for you: http://cinjweb.umdnj.edu/~kerrigje/pdf_files/NAMD-LIE-tutorial.pdf

Hope that help,

Radif

Thanks Danish and Muhammad for valuable informations.

So, right now I have 100 ns equilibrated structures of all the systems (WT and the mutants). There are conformational changes happening during the simulations of the ligand-free systems. Now to dock the ligand molecules in these systems I need to delete few portions of a loop that penetrates inside the ligand binding pocket. This would eventually dismiss the possibility of steric clash.

I think your wish to study the efefct of mutation on ligand binding. I would like you go through this article which will give you an idea about all analysis and will help you in go forward with the project. Link here: https://www.researchgate.net/publication/263130935_An_integrated_molecular_dynamics_principal_component_analysis_and_residue_interaction_network_approach_reveals_the_impact_of_M184V_mutation_on_HIV_reverse_transcriptase_resistance_to_lamivudine

Article An Integrated Molecular Dynamics, Principal Component Analys...