A new hydrogen-bonding potential for the design of protein-RNA interactions predicts specific contacts and discriminates decoys

TitleA new hydrogen-bonding potential for the design of protein-RNA interactions predicts specific contacts and discriminates decoys
Publication TypeJournal Article
Year of Publication2004
AuthorsChen, Y., Kortemme T., Robertson T., Baker D., & Varani G.
JournalNucleic acids research
Volume32
Issue17
Pagination5147-62
Date Published2004
ISSN1362-4962
KeywordsAmino Acid Sequence, Binding Sites, Collaborative Publication, Computational Biology, Data Interpretation, Statistical, Databases, Protein, DNA-Binding Proteins, Hydrogen Bonding, Models, Molecular, Molecular Structure, Protein Binding, RNA, RNA-Binding Proteins
Abstract

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.

Alternate JournalNucleic Acids Res.
AttachmentSize
chen04.pdf1.47 MB