ART-RRT: As-Rigid-As-Possible exploration of ligand unbinding pathways

Area of Science:

• Computational Chemistry
• Molecular Dynamics
• Computer Graphics

Background:

• Determining ligand unbinding pathways is crucial for understanding drug efficacy and molecular interactions.
• Existing methods often require computationally expensive simulations or predefined reaction coordinates.

Purpose of the Study:

• To develop an efficient and versatile method for generating approximate ligand unbinding pathways.
• To provide a computationally inexpensive alternative to traditional pathway exploration techniques.

Main Methods:

• Combines a tree-based exploration algorithm with a computer graphics morphing technique for dimensionality reduction.
• Does not require a predefined reaction coordinate, allowing for flexible pathway searching.
• Evaluated on multiple benchmark systems.

Main Results:

• The proposed method is time-efficient and computationally inexpensive.
• Generated pathways show good agreement with state-of-the-art approaches.
• Successfully identifies pathways regardless of prior knowledge of their direction.

Conclusions:

• The developed method offers an efficient approach for approximating ligand unbinding pathways.
• These approximate pathways can serve as starting points for more detailed analyses or specialized simulations.
• The technique enhances the feasibility of exploring molecular unbinding mechanisms.