Adaptive BP-Dock: An Induced Fit Docking Approach for Full Receptor Flexibility

We
present an induced fit docking approach called Adaptive BP-Dock
that integrates perturbation response scanning (PRS) with the flexible
docking protocol of RosettaLigand in an adaptive manner. We first
perturb the binding pocket residues of a receptor and obtain a new
conformation based on the residue response fluctuation profile using
PRS. Next, we dock a ligand to this new conformation by RosettaLigand,
where we repeat these steps for several iterations. We test this approach
on several protein test sets including difficult unbound docking cases
such as HIV-1 reverse transcriptase and HIV-1 protease. Adaptive BP-Dock
results show better correlation with experimental binding affinities
compared to other docking protocols. Overall, the results imply that
Adaptive BP-Dock can easily capture binding induced conformational
changes by simultaneous sampling of protein and ligand conformations.
This can provide faster and efficient docking of novel targets for
rational drug design.