SIM-XL

SIM-XL is a software tool that analyzes cross-linked peptides obtained through chemical cross-linking experiments and tandem mass spectrometry. It addresses the challenge of correctly identifying covalently linked peptides by introducing a new approach to reduce the search space, improving speed and sensitivity. The software utilizes reporter ions to select tandem mass spectra derived from cross-linked peptides, a feature not present in other tools. Additionally, SIM-XL provides a 2D interaction map and a spectrum-annotation tool that are unmatched by similar software. Comparative analysis using a dataset from the human HSP90 protein demonstrates that SIM-XL outperforms a competing tool in terms of sensitivity and speed. The software is freely available for academic use, and a video explaining its functionality is provided. SIM-XL is the first tool to support XL data in the mzIdentML format, and all data are accessible through the ProteomeXchange consortium.