chiLife: An open-source Python package for in silico spin labeling and integrative protein modeling

Abstract

Here 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.

Ultrafast Bioorthogonal Spin-Labeling and Distance Measurements in Mammalian Cells Using Small, Genetically Encoded Tetrazine Amino Acids

“…To test if our Tet4-based spin-labeling system was capable of discerning the maltose-driven clamshell conformational change, we recorded DEER on doubly Tet4-Ph-encoded MBP constructs spin-labeled with sTCO-nitroxides, both in the presence and in the absence of maltose (Figures D,F, S12, and S13). Distance distributions obtained for apo and maltose-bound MBP211/295–Tet4-Ph labeled with sTCO-tE5 were in reasonable agreement with predictions from in silico rotameric modeling and displayed significantly broader distributions compared to the MTSL-labeled constructs (Figure D). Nevertheless, a clear shift toward shorter interspin distances was observed in the sample containing 5 mM maltose, consistent with the maltose-induced closure of MBP.…”

Revealing light-induced structural shifts in G-quadruplex-porphyrin complexes: a pulsed dipolar EPR study

“…In this work, all possible spin label rotamers were calculated using an open-source Python library ChiLife. 82,83 Thanks to its script-based nature, ChiLife can be easily integrated with other Python packages, such as MDAnalysis 84 and Autodock Vina. 85…”

Measuring conformational equilibria in allosteric proteins with time-resolved tmFRET

“…The values of the average distances and standard deviations in the apo and holo states for 14 different experiments are shown in a spaghetti plot in Figure2B and a scatter plot in Figure 2C and were very reproducible. To compare our data to the predictions of structural modeling, rotameric ensembles of Acd and [Ru(bpy) 2 phenM] 2+ were modelled onto crystal structures of apo and holo MBP (19,20) using the accessible-volume approach in chiLife (21), and used to predict distance distributions for MBP-322Acd-278C labeled with [Ru(bpy) 2 phenM] 2+ (Figure 2B). In both the absence and presence of maltose, the distance distributions were remarkably similar to those predicted by chiLife.…”

“…Computational modeling of Acd and metal-phenM labels, as well as distance distribution predictions, were performed using chiLife (21) with the accessible-volume sampling method (34,35). Acd, and cysteine conjugates of [Ru(bpy…”