I have been writing a script with PyRosetta to investigate the interactions of mutant enzyme poses with a small molecule ligand. To dock the ligand into the enzyme's binding site, I've started with a pose where the ligand is placed in the vicinity of the binding position, and then I run the DockMCMProtocol. However, this docking protocol seems to indiscriminately change the position of the ligand within the binding pocket. Very rarely does the ligand "lock" in to the catalytic residues, and every so often a tested mutation will cause a side chain to occlude the opening of the binding pocket and the subsequent docking runs shocklingly result in an improved interaction energy!
I was wondering if anyone knew of a more appropriate method for local small molecule ligand docking in PyRosetta -- perhaps one that includes more dynamics considerations for the ligand entering and traversing through the binding pocket. I know that in Autodock Vina, you define a cube-shaped region through which the ligand can be docked. Is there something that's somewhat similar in PyRosetta? Any input would be appreciated!