Section: New Results

ART-RRT: As-Rigid-As-Possible Exploration of Ligand Unbinding Pathways

Participants : Minh Khoa Nguyen, Jaillet Leonard, Stephane Redon.

We proposed a method to efficiently generate approximate ligand unbinding pathways (to appear in the Journal of Computational Chemistry). It combines an efficient tree-based exploration method with a morphing technique from Computer Graphics for dimensionality reduction. This method is computationally cheap and, unlike many existing approaches, does not require a reaction coordinate to guide the search. It can be used for finding pathways with known or unknown directions beforehand. The approach is evaluated on several benchmarks and the obtained solutions are compared with the results from other state-of-the-art approaches. We show that the method is time-efficient and produces pathways in good agreement with other state-of-the-art solutions. These paths can serve as first approximations that can be used, analyzed or improved with more specialized methods.

Figure 6. Paths (in colored sticks) obtained by ART-RRT for the unbinding of retinoic acid hormone from its receptor. The protein is represented by ribbons and the ligand by orange balls. Two different views are shown for clarity. The left picture shows pathways I in red, II in blue, III in green and Other in black. The right picture shows pathways IV in yellow, V in purple and VI in cyan. These main pathways are also reported by other studies by the SMD and RAMD methods for nuclear hormone receptors.