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

Adam Belsom, Michael Schneider, Lutz Fischer, Mahmoud Mabrouk, Kolja Stahl, Oliver Brock, Juri Rappsilber

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
JournalWellcome Open Research
DOIs
Publication statusPublished - 13 Mar 2017

Keywords

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

Fingerprint

Dive into the research topics of 'Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11)'. Together they form a unique fingerprint.

Cite this