chiLife: An open-source Python package forin silicospin labeling and integrative protein modeling

Abstract

AbstractHere we introduce chiLife, a Python package for site-directed spin label (SDSL) modeling for electron paramagnetic resonance (EPR) spectroscopy, in particular double electron–electron resonance (DEER). It is based on in silico attachment of rotamer ensemble representations of spin labels to protein structures. chiLife enables the development of custom protein analysis and modeling pipelines using SDSL EPR experimental data. It allows the user to add custom spin labels, scoring functions and spin label modeling methods. chiLife is designed with integration into third-party software in mind, to take advantage of the diverse and rapidly expanding set of molecular modeling tools available with a Python interface. This article describes the main design principles of chiLife and presents a series of examples.Author summaryThanks to modern modeling methods like AlphaFold2, RosettaFold, and ESMFold, high-resolution structural models of proteins are widely available. While these models offer insight into the structure and function of biomedically and technologically significant proteins, most of them are not experimentally validated. Furthermore, many proteins exhibit functionally important conformational flexibility that is not captured by these models. Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy is a powerful tool for probing protein structure and conformational heterogeneity, making it ideal for validating, refining, and expanding protein models. To extract quantitative protein backbone information from experimental SDSL EPR data, accurate modeling methods are needed. For this purpose, we introduce chiLife, an open-source Python package for SDSL modeling designed to be extensible and integrable with other Python-based protein modeling packages. With chiLife, appropriate SDSL EPR experiments for protein model validation can be designed, and protein models can be refined using experimental SDSL EPR data as constraints.