A free energy pathway for the interaction of the SRY protein with its binding site on DNA from atomistic simulations.
The SRY gene on the Y chromosome is a necessary and sufficient condition for the development of the male phenotype and is involved in sex-reversal pathologies. The associated SRY protein also represents a convenient model system for the study of indirect protein-DNA recognition mechanisms, in which the local plasticity of DNA may play a more important role than direct interactions between the protein and the DNA bases. Using a novel, low-bias restraint methodology, we have performed molecular dynamics simulations of the controlled dissociation of SRY from its cognate DNA sequence. The resulting free energy profile provides a detailed view of protein-DNA binding and identifies a metastable intermediate state.
Bouvier
Benjamin
B
Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS. 7, passage du Vercors, F-69007 Lyon, France. benjamin.bouvier@ibcp.fr
Lavery
Richard
R
D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D024742:HMG-Box Domains; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D051876:Sex-Determining Region Y Protein / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
D051876:Sex-Determining Region Y Protein; D004247:DNA