A free energy pathway for the interaction of the SRY protein with its binding site on DNA from atomistic simulations

J Am Chem Soc. 2009 Jul 29;131(29):9864-5. doi: 10.1021/ja901761a.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA / chemistry*
  • DNA / metabolism*
  • HMG-Box Domains
  • Models, Molecular
  • Protein Structure, Secondary
  • Sex-Determining Region Y Protein / chemistry*
  • Sex-Determining Region Y Protein / metabolism*
  • Thermodynamics

Substances

  • Sex-Determining Region Y Protein
  • DNA