Improved cross-linking models between amino acids with DynamXL software

The structure of a protein informs us about the potential functions of the components of the protein, its relationship with other molecules and its physiological relevance. Identifying cross-links (or covalent links) between amino acids in a protein is crucial to establish the structure of protein assemblies and the association between the subunits.

Oxford researchers have developed software that can more precisely model cross-links between amino acids in a protein by accounting for the dynamics of the linker and amino acid side chains. Models generated from this software can be used to more accurately determine protein structures and significantly improve protein-protein docking.

Structure matters

The growth of systems and structural biology has led to an increasing need to analyse more complex systems faster and with increasing accuracy.  Many diseases are consequences of altered functionality due to altered protein structures. A high-resolution protein structure can greatly improve our understanding of the operating mechanism of that protein and how alterations impact its functions. Furthermore, information about a protein structure can support the discovery and development of drugs that specifically target the protein.

Vital insight

Chemical cross-linking coupled with mass spectrometry (XL-MS) is a revolutionary approach in structural biology that can help identify cross-links between amino acid side chains. It can provide vital insight into both the structure and organization of proteins in a wide variety of conditions, including in solution. Existing algorithms that simulate cross-links for a given atomistic protein structure are highly error-prone. They fail to take important parameters, for example, the dynamics of amino acid side chains, into consideration.

Dramatic increase in accuracy

Researchers at the University of Oxford have developed software that accounts for alternative orientations of the linker and amino acid side chains and large-scale protein conformational changes. The result is dramatically increased precision of protein structure models.

The software also:

  • Outperforms existing approaches in interpreting XL-MS data
  • Can be performed on an ensemble of alternative atomic arrangements
  • Can deal with structural ensembles from various sources (NMR, X-ray crystallography and molecular dynamics etc.)
  • Allows significant improvements in protein-protein docking
  • Has been validated through exhaustive benchmarking
  • Is capable of accommodating motions at both reactive side-chain levels and large-scale rearrangements of the protein backbone

This software represents a considerable increase in the obtainable structural insights attainable using chemical cross-linking.

Oxford University Innovation is interested to speak with companies who would like to license this software to enhance their strategies for resolving protein structures.

DynamXL is part of the Oxford Protein Analysis Software Suite (OxPASS), which provides the means to collate data from Mass Spectrometry, NMR and X-Ray crystallography experiments with unprecedented speed and accuracy. Click here for more information.

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