RinPy, a Python Package for Residue Interaction Network Model to Analyze Protein Structures and Predict Ligand...

The residue interaction network (RIN) model has been a useful approach for identifying functional residues and ligand-binding sites in different protein structures based on their contact topology. Here, we present RinPy, a pip-installable Python package, and a graphical user interface (GUI) that depends on a RIN model. RinPy is designed for constructing, visualizing, and analyzing RINs for single or multiple protein input structures as well as molecular dynamics trajectories, allowing the calculation of three centrality measures, namely degree, closeness, and betweenness of the residues. The nodes with the highest betweenness scores are used to suggest putative allosteric sites, and the graph spectral analysis provides hinge regions linking close-neighboring clusters. The program is enhanced using a multiprocessing module to enable efficient analysis of large protein structures and employing user-defined parameters necessary for network analysis. The package supports the integration of nucleotides, cofactors, small molecules, water, and ions directly into the network analysis, which may be highly beneficial to understand the functional interactions in protein complexes. The program consists of numerous modules producing multiple outputs, including interactive visualizations to facilitate interpretation of the results. It also provides comparative network analysis to quantify how perturbations, such as ligand binding or mutations, may alter the contact topology of protein complexes. RinPy is implemented to a data set of monomeric KRAS and KRAS-SOS1 complexes as a case study, demonstrating its ability to identify known functional and allosteric site residues and highlighting its rapid calculation and analysis of RINs. The RinPy package is compatible with Windows, macOS, and Linux operating systems. RinPy is an open-source Python package distributed via the Python Package Index (PyPI) under the name rinpy, with its source code available on GitHub. The RinPy GUI is also available as a standalone executable for Windows.