A new hydrogen-bonding potential for the design of protein-RNA interactions predicts specific contacts and discriminates decoys.
RNA-binding proteins play many essential roles in the regulation of gene expression in the cell. Despite the significant increase in the number of structures for RNA-protein complexes in the last few years, the molecular basis of specificity remains unclear even for the best-studied protein families. We have developed a distance and orientation-dependent hydrogen-bonding potential based on the statistical analysis of hydrogen-bonding geometries that are observed in high-resolution crystal structures of protein-DNA and protein-RNA complexes. We observe very strong geometrical preferences that reflect significant energetic constraints on the relative placement of hydrogen-bonding atom pairs at protein-nucleic acid interfaces. A scoring function based on the hydrogen-bonding potential discriminates native protein-RNA structures from incorrectly docked decoys with remarkable predictive power. By incorporating the new hydrogen-bonding potential into a physical model of protein-RNA interfaces with full atom representation, we were able to recover native amino acids at protein-RNA interfaces.
Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Yu
Y
Chen
Tanja
T
Kortemme
Tim
T
Robertson
David
D
Baker
Gabriele
G
Varani
D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D003627:Data Interpretation, Statistical; D030562:Databases, Protein; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D012313:RNA