Edinburgh Research Explorer

Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11)

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions



  • Download as Adobe PDF

    Accepted author manuscript, 6.77 MB, PDF document

  • Download as Adobe PDF

    Rights statement: This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Final published version, 5.02 MB, PDF document

    Licence: Creative Commons: Attribution (CC-BY)

Original languageEnglish
JournalWellcome Open Research
Publication statusPublished - 13 Mar 2017


Determining the structure of a protein by any method requires various contributions from experimental and computational sides. In a recent study, high-density crosslinking/ mass spectrometry (HD-CLMS) data in combination with ab initio structure prediction determined the structure of human serum albumin (HSA) domains, with an RMSD to X-ray structure of up to 2.5 Å, or 3.4 Å in the context of blood serum. This paper reports the blind test on the readiness of this technology through the help of Critical Assessment of protein Structure Prediction (CASP). We identified between 201- 381 unique residue pairs at an estimated 5% FDR (at link level albeit with missing site assignment precision evaluation), for four target proteins. HD-CLMS proved reliable once crystal structures were released. However, improvements in structure prediction using cross-link data were slight. We identified two reasons for this. Spread of crosslinks along the protein sequence and the tightness of the spatial constraints must be improved. However, for the selected targets even ideal contact data derived from crystal structures did not allow modellers to arrive at the observed structure. Consequently, the progress of HD-CLMS in conjunction with computational modeling methods as a structure determination method, depends on advances on both arms of this hybrid approach.

    Research areas

  • High-density cross-linking/mass spectrometry, chemical biology, protein cross-linking, Protein Structure, CASP, structural biology, computational biology, protein modeling

Download statistics

No data available

ID: 35256178