Cross(X)link Mapping and AnalySis (XMAS) – Smooth Integrative Modeling in ChimeraX

Abstract

Crosslinking mass spectrometry (XL-MS) has demonstrated its ability to add tremendous value to structural biology investigations. Its main strength lies in uncovering structural information from proteins in the form of distance constraints between neighboring amino acids, even in particularly complex samples containing proteins with regions difficult to access by other techniques. However, interpreting XL-MS data in a structural context has been cumbersome, even though several approaches have been developed. Moreover, with the introduction of the highly flexible and widely used ChimeraX – a software package for visualization of structural data – XL-MS analysis tools previously available in its predecessor, Chimera, were lost. We therefore introduce XMAS, a bundle for ChimeraX that allows users to load results from several XL-MS search engines straight into ChimeraX and directly map the information onto protein structures. Besides automatically locating the distance constraints on the protein structure, XMAS offers the possibility to work with replicate experiments and/or different crosslinkers, and filter on reproducibility of distance constraints across replicates to increase the data quality. We additionally introduce the concept of self-links, which allows modeling of homomeric interactions. Furthermore, we implemented a seamless connection to the structural modeling suite of HADDOCK to ease difficult tasks in the structural modeling pipeline. Here, key functionalities of XMAS are demonstrated on data obtained from human fibrin clots. The software is freely available from the ChimeraX toolshed, with an extensive user manual for quickly grasping the functionality.