Extending the applicability of the O-ring theory to protein-DNA complexes

Comput Biol Chem. 2013 Jun;44:31-9. doi: 10.1016/j.compbiolchem.2013.02.005. Epub 2013 Mar 14.

Abstract

Many biological processes depend on protein-based interactions, which are governed by central regions with higher binding affinities, the hot-spots. The O-ring theory or the "Water Exclusion" hypothesis states that the more deeply buried central regions are surrounded by areas, the null-spots, whose role would be to shelter the hot-spots from the bulk solvent. Although this theory is well-established for protein-protein interfaces, its applicability to other protein interfaces remains unclear. Our goal was to verify its applicability to protein-DNA interfaces. We performed Molecular Dynamics simulations in explicit solvent of several protein-DNA complexes and measured a variety of solvent accessible surface area (SASA) features, as well as, radial distribution functions of hot-spots and null-spots. Our aim was to test the influence of water in their coordination sphere. Our results show that hot-spots tend to have fewer water molecules in their neighborhood when compared to null-spots, and higher values of ΔSASA, which confirms their occlusion from solvent. This study provides evidence in support of the O-ring theory with its applicability to a new type of protein-based interface: protein-DNA.

MeSH terms

  • Algorithms
  • Computational Biology
  • DNA / chemistry*
  • Databases, Protein
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • Proteins / chemistry*

Substances

  • Proteins
  • DNA