title: Extending the applicability of the O-ring theory to protein-DNA complexes.
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.
authors.affiliation: REQUIMTE/Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
authors.forename: R M
authors.initials: RM
authors.lastname: Ramos
authors.forename: L F
authors.initials: LF
authors.lastname: Fernandes
authors.forename: I S
authors.initials: IS
authors.lastname: Moreira
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D004247:DNA / Q000737:chemistry*; D030562:Databases, Protein; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins; D004247:DNA