I made a homology model base on a template structure (>70% alignment) using MODELLER 10.5. The homology model is used for drug docking study, so I check the side chain orientations at the active site and notice some difference between sidechain orientations of the homology model and the template.
I check the non-covalent interactions these side chain have around 5A and is considering modify the orientation of sidechains in my homology model base on the orientations in the template. Is this a good idea? Because I know MODELLER perform an auto energy minimization of the structure, so I'm hesitating on manually modifying the side chain orientations.
I'm very new to drug docking and homology modelling. Thank you in advance! Any help would be greatly appreciated!
Edit on July 5th:
I solved my problem. For any one who also want to use MODELLER in the future, I look into MODELLER manual section 2.2.1 and modelled water and ligand molecules into my homology model (my X-ray template structure include coordinations of water and ligand molecules). In the new models, all the aligned resides at the active site have similar side chain orientations.
Are the active site residues are same? if not then how you can expect them to be in the same orientation to that of template. Do you have any gaps in or around active site? try to shift the gap if any gap is there. Create a multi-template model and then compare if the new model also has the same probelm.
Does MODELLER include a side-chain optimization step after it produces a homology model? If not, you could do a side chain optimization. You could also optimize the hydrogen-bonding network.
Rudy J Richardson Thank you for answering my question! I've got my problem solved. MODELLER does include a side-chain optimization step.
Ayaz Anwar Thank you as well! The active site residues are the same that's why I was frustrated about the different orientations. But I got my problem solved by including the modelling of water molecules in the X ray template structure to the homology model.
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