1. Learning Protein-Ligand Unbinding Pathways via Single-Parameter Community Detection.
- Author
-
Tänzel V, Jäger M, and Wolf S
- Subjects
- Ligands, Biotin chemistry, Streptavidin chemistry, Algorithms, Protein Binding, Triazoles chemistry, Humans, Receptor, Adenosine A2A metabolism, Receptor, Adenosine A2A chemistry, Molecular Dynamics Simulation
- Abstract
Understanding the dynamics of biomolecular complexes, e.g., of protein-ligand (un)binding, requires the comprehension of paths such systems take between metastable states. In MD simulations, paths are usually not observable per se, but they need to be inferred from simulation trajectories. Here, we present a novel approach to cluster trajectories based on a community detection algorithm that necessitates only the definition of a single parameter. The unbinding of the streptavidin-biotin complex is used as a benchmark system and the A
2a adenosine receptor in complex with the inhibitor ZM241385 as an elaborate application. We demonstrate how such clusters of trajectories correspond to pathways and how the approach helps in the identification of reaction coordinates for a considered (un)binding process.- Published
- 2024
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