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Classical molecular dynamics simulations of the complex between the RAD51 protein and the BRC hairpin loops of the BRCA2 protein

  • Nick Buis
    ,
  • Chris Kriton Skylaris
    ,
  • Guy H. Grant
    ,
  • Eeson Rajendra
    ,
  • Mike C. Payne
    ,
  • Ashok R. Venkitaraman
  • University of Cambridge
    ,
  • University of Southampton
Research Output: Contribution to journal Article Peer-review

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

In the repair of double-strand breaks of DNA by homologous recombination the recombinase protein RAD51 has its functions controlled by the breast cancer susceptibility protein BRCA2. BRCA2 can bind to RAD51 via the BRC repeats BRC1–BRC8, which are eight conserved sequence motifs in BRCA2 of about 35 amino acids. We have carried out a series of extensive unrestrained atomistic molecular dynamics (MD) simulations in explicit water for a total time period of 248 ns, in order to study the dynamical behaviour and conformations of the complexes between the hairpin loop region of the BRC repeats and RAD51. Our simulations have allowed us to investigate the conformations adopted by the BRC repeats both while bound to RAD51 and while isolated. These conformations are rationalised through an analysis of the inter- and intra-molecular backbone and side chain bonding interactions in all the eight human BRC repeats as well as in a single-point mutation of BRC4. The differences in sequence result in differences in the interactions between the BRC repeats and the RAD51 protein but these do not appear to disrupt the binding in any of the BRC–RAD51 complexes as there are always a number of key residues remaining which allow a sufficient number of interactions to stabilise the complexes.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 749-759 (11 pages)

Journal (Volume, Issue Number)

Molecular Simulation (Volume 34, Issue 8)

Publication milestones

  • Published - 01/08/2008

Publication status

Published - 01/08/2008

ISSN

0892-7022

External Publication IDs

  • handle.net: 10547/228913
  • Scopus: 49649088827

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