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Accommodating Protein Dynamics in the Modeling of Chemical Crosslinks.

Authors
  • Degiacomi, Matteo T1
  • Schmidt, Carla2
  • Baldwin, Andrew J2
  • Benesch, Justin L P3
  • 1 Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK. Electronic address: [email protected]
  • 2 Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
  • 3 Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK. Electronic address: [email protected]
Type
Published Article
Journal
Structure
Publisher
Elsevier
Publication Date
Nov 07, 2017
Volume
25
Issue
11
Identifiers
DOI: 10.1016/j.str.2017.08.015
PMID: 28966018
Source
Medline
Keywords
License
Unknown

Abstract

Chemical crosslinking can identify the neighborhood relationships between specific amino-acid residues in proteins. The interpretation of crosslinking data is typically performed using single, static atomic structures. However, proteins are dynamic, undergoing motions spanning from local fluctuations of individual residues to global motions of protein assemblies. Here we demonstrate that failure to explicitly accommodate dynamics when interpreting crosslinks structurally can lead to considerable errors. We present a method and associated software, DynamXL, which is able to account directly for flexibility in the context of crosslinking modeling. Our benchmarking on a large dataset of model structures demonstrates significantly improved rationalization of experimental crosslinking data, and enhanced performance in a protein-protein docking protocol. These advances will provide a considerable increase in the structural insights attainable using chemical crosslinking coupled to mass spectrometry.

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