AnchorMS: a bioinformatics tool to derive structural information from the mass spectra of cross-linked protein complexes

Abstract

Mass spectrometry is being increasingly used in the structural elucidation of mega-Dalton protein complexes in an approach termed MS3D, referring to the application of MS to the study of macromolecular structures. This involves the identification of cross-linked residues in the constituent proteins of chemically cross-linked multi-subunit complexes. AnchorMS was developed to simplify MS3D studies by identifying cross-linked peptides in complex peptide mixtures, and to determine the specific residues involved in each cross-link. When identifying cross-linked peptide pairs (CLPP), AnchorMS implements a mathematical model to exclude false positives by using a dynamic score threshold to estimate the number of false-positive peak matches expected in an MS/MS spectrum. This model was derived from CLPPs with randomly generated sequences. AnchorMS does not require specific sample labeling or pre-treatment, and AnchorMS is especially suited for discriminating between CLPPs that differ only in the cross-linked residue pairs. AnchorMS was coded in Python, and is available as a free web service at cbio.ufs.ac.za/AnchorMS.