title: Protein Dynamics and Contact Topology Reveal Protein-DNA Binding Orientation.
abstract: Structure-encoded conformational dynamics are crucial for biomolecular functions. However, there is insufficient evidence to support the notion that dynamics play a role in guiding protein-nucleic acid interactions. Here, we show that protein-DNA docking orientation is a function of protein intrinsic dynamics, but the binding site itself does not display unique patterns in the examined spectrum of motions. This revelation is made possible by a novel technique that locates "dynamics interfaces" in proteins across which protein parts are anticorrelated in their slowest dynamics. A striking statistic is that such interfaces intersect the DNA in 97% of the 104 examined cases. These findings were then used to screen decoys generated by rigid-body docking of DNA molecules onto DNA-binding proteins. Using our method, the chance to discern near-native poses from non-native decoys increased by 2.5- and 1.6-fold, as compared to a random guess and methods based on surface complementarity, respectively. Hence, dynamically allowed protein-DNA docking orientations can work as new filters to cull and rerank docking poses and therefore enhance the predictability of DNA-binding sites that themselves do not have distinct dynamics features. Computer software implementing the method can be accessed via http://dyn.life.nthu.edu.tw/IDD/DNA.htm .
authors.forename: Aravind
authors.initials: A
authors.lastname: Chandrasekaran
authors.forename: Justin
authors.initials: J
authors.lastname: Chan
authors.forename: Carmay
authors.initials: C
authors.lastname: Lim
authors.affiliation: Physics Division, National Center for Theoretical Sciences , Hsinchu 30013, Taiwan.
authors.forename: Lee-Wei
authors.initials: LW
authors.lastname: Yang
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019277:Entropy; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA