Papers › Self-Organizing Maps of Unbiased Ligand-Target Binding Pathways and Kinetics
Self-Organizing Maps of Unbiased Ligand-Target Binding Pathways and Kinetics
Lara Callea, Camilla Caprai, Laura Bonati, Toni Giorgino, Stefano Motta
The interpretation of ligand-target interactions at atomistic resolution is central to most efforts in computational drug discovery and optimization. However, the highly dynamic nature of protein targets, as well as possible induced fit effects, makes difficult to sample many interactions effectively with docking studies or even with large-scale molecular dynamics (MD) simulations. We propose a novel application of Self-Organizing Maps (SOM) to address the sampling and dynamic mapping tasks, particularly in cases involving ligand flexibility and induced fit. The SOM approach offers a data-driven strategy to create a map of the interaction process and pathways based on unbiased MD. Furthermore, we show how the preliminary SOM mapping is complementary to kinetic analysis, both with the employment of network-based approaches and Markov State Models (MSM). We demonstrate the method by comprehensively mapping a large dataset of 640 {\mu}s of unbiased trajectories sampling the recognition process between the phosphorylated YEEI peptide and its high-specificity target Lck-SH2. The integration of SOM into unbiased simulation protocols significantly advances our understanding of the ligand binding mechanism. This approach serves as a potent tool for mapping intricate ligand-target interactions with unprecedented detail, thereby enhancing the characterization of kinetic properties crucial to drug design.
Code
No code repository is listed for this paper in the archive or in Syntology's graph.
Code Syntology ran Syntology
Not run by Syntology. Nothing on this page verifies that the listed code works.
Tasks
Datasets
Introduced by this paper, per the archive.
Results from the paper archive 2025-07-28
No leaderboard rows for this paper in the archive.
Methods
Report a problem or propose a change · a person checks every report against the paper or source before anything changes; decisions are listed on /corrections