Hi,
I am doing molecular docking using a 3D structure from PDB. This structure is from the rat protein but I would like to make sure the human protein would give the same results. Only two amino-acids are different in the active site between human and rat (ILE instead of VAL in both cases). Is it possible to generate a 3D structure from the rat protein with these two mutations (VAL to ILE) ?
which software should I use ? Autodock?
Thanks for your help.
Julien
Hi Julien,
Sometimes distal mutations can still perturb the binding site, so if no human structure is available I would consider using an AlphaFold prediction. If rat-human sequence identity is high, a homology model built in e.g. MODELLER or Swiss‑Model is typically very reliable and they include energy minimization steps to refine backbone and side‑chain geometry.
To focus on the active site, PyMOL’s Mutagenesis wizard lets you mutate residues in the active site, choosing among multiple rotamers with their estimated probabilities to avoid and see obvious clashes. Since your active site seems very conserved it could be a quicker, more approximate approach.
AutoDock4 and Vina have good performances. In my understanding, there is no absolute best docking engine. It is system dependant as they each employ distinct scoring functions. Consensus docking across several engines would be the ideal way to mitigate scoring bias, although it is rarely practical.
Raphael
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