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

Classical molecular dynamics simulations of the complex between the RAD51 protein and the BRC hairpin loops of the BRCA2 protein
Classical molecular dynamics simulations of the complex between the RAD51 protein and the BRC hairpin loops of the BRCA2 protein
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.
molecular dynamics, proteins, BRCA2, RAD51
749-759
Buis, Nick
6bcceeb0-5393-48c8-938e-927d9d639d48
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61
Grant, Guy
a75c6ec2-63a0-4ccb-bbd0-5887f51c1993
Rajendra, Eeson
ab2f270e-caf8-4c9a-ab99-247e55517fce
Payne, Mike
bb065804-2558-471b-ad21-afdfd4889f11
Venkitaraman, Ashok
80aba618-37ce-42e2-8905-1f6ffbdf7244
Buis, Nick
6bcceeb0-5393-48c8-938e-927d9d639d48
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61
Grant, Guy
a75c6ec2-63a0-4ccb-bbd0-5887f51c1993
Rajendra, Eeson
ab2f270e-caf8-4c9a-ab99-247e55517fce
Payne, Mike
bb065804-2558-471b-ad21-afdfd4889f11
Venkitaraman, Ashok
80aba618-37ce-42e2-8905-1f6ffbdf7244

Buis, Nick, Skylaris, Chris-Kriton, Grant, Guy, Rajendra, Eeson, Payne, Mike and Venkitaraman, Ashok (2008) Classical molecular dynamics simulations of the complex between the RAD51 protein and the BRC hairpin loops of the BRCA2 protein. Molecular Simulation, 34 (8), 749-759. (doi:10.1080/08927020802213281).

Record type: Article

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.

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Published date: July 2008
Keywords: molecular dynamics, proteins, BRCA2, RAD51
Organisations: Chemistry

Identifiers

Local EPrints ID: 149275
URI: https://eprints.soton.ac.uk/id/eprint/149275
PURE UUID: b029219c-7be8-49bd-a3c4-e870d29be8a7
ORCID for Chris-Kriton Skylaris: ORCID iD orcid.org/0000-0003-0258-3433

Catalogue record

Date deposited: 12 Jul 2010 10:35
Last modified: 17 Jul 2018 00:32

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