PocketMaster: a flexible, automated tool for analyzing, clustering, and visualizing protein pocket structural diversity

Abstract

PocketMaster is a flexible and automated tool for the analysis, clustering, and interpretation of protein pockets. It enables the exploration of structural diversity in functional and interacting regions of proteins, supports scalable alignment, RMSD calculation, and hierarchical clustering of hundreds to thousands of models. The tool provides multiple pocket-detection methods, alignment algorithms, and clustering approaches, allowing analyses to be tailored to specific scientific questions. With these capabilities, PocketMaster can be particularly valuable in the early stages of drug design, where accurate analysis and selection of protein structures are essential. Using TYK2 as a case study, PocketMaster demonstrated its ability to identify conformational differences between kinase and pseudokinase domains, as well as subtypes of structures within each domain, reflecting the influence of various ligands and protein states. The results confirm known structural features and illustrate the potential of the tool for systematic exploration of protein pockets, quantitative assessment of differences, and support of rational drug design. The PocketMaster source code, together with example input files and documentation, can be accessed at https://github.com/narek-abelyan/PocketMaster