Combining Information from Crosslinks and Monolinks in the Modelling of Protein Structures

Monolinks are produced in a Chemical Crosslinking Mass Spectrometry experiment and are more abundant than crosslinks. They convey residue exposure information, but so far have not been used in the modelling of protein structures. Here we present the Monolink Depth Score (MoDS), for assessing structural models based on the depth of monolinked residues, corresponding to their distance to the nearest bulk water. Using simulated and reprocessed experimental data from the Proteomic Identification Database, we compare the performance of MoDS to MNXL - our previously-developed score for assessing models based on crosslinking data. Our results show that MoDS can be used to effectively score model structures based on monolinks, and that combining it with MNXL leads to overall higher scoring performance. The work strongly supports the use of monolink data in the context of integrative structure determination. We also present XLM- Tools, a programme to assist in this effort, available at: https://github.com/Topf-Lab/XLM-Tools.

Keywords: XLMS, Crosslinks, Monolinks, Residue Depth, Protein Structure Modelling

Suggested Citation: Suggested Citation

Sinnott, Matthew and Malhotra, Sony and Madhusudhan, Mallur Srivatsan and Thalassinos, Konstantinos and Topf, Maya, Combining Information from Crosslinks and Monolinks in the Modelling of Protein Structures. Available at SSRN: https://ssrn.com/abstract=3569541 or http://dx.doi.org/10.2139/ssrn.3569541

This version of the paper has not been formally peer reviewed.