title: Probing binding hot spots at protein-RNA recognition sites.
abstract: We use evolutionary conservation derived from structure alignment of polypeptide sequences along with structural and physicochemical attributes of protein-RNA interfaces to probe the binding hot spots at protein-RNA recognition sites. We find that the degree of conservation varies across the RNA binding proteins; some evolve rapidly compared to others. Additionally, irrespective of the structural class of the complexes, residues at the RNA binding sites are evolutionary better conserved than those at the solvent exposed surfaces. For recognitions involving duplex RNA, residues interacting with the major groove are better conserved than those interacting with the minor groove. We identify multi-interface residues participating simultaneously in protein-protein and protein-RNA interfaces in complexes where more than one polypeptide is involved in RNA recognition, and show that they are better conserved compared to any other RNA binding residues. We find that the residues at water preservation site are better conserved than those at hydrated or at dehydrated sites. Finally, we develop a Random Forests model using structural and physicochemical attributes for predicting binding hot spots. The model accurately predicts 80% of the instances of experimental ΔΔG values in a particular class, and provides a stepping-stone towards the engineering of protein-RNA recognition sites with desired affinity.
authors.affiliation: Computational Structural Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Barik
authors.affiliation: Computational Structural Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.
authors.forename: Chandran
authors.initials: C
authors.lastname: Nithin
authors.affiliation: Advanced Technology Development Centre, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.
authors.forename: Naga Bhushana Rao
authors.initials: NB
authors.lastname: Karampudi
authors.affiliation: Computational Structural Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.
authors.forename: Sunandan
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Computational Structural Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India Advanced Technology Development Centre, Indian Institute of Technology Kharagpur, Kharagpur-721302, India r.bahadur@hijli.iitkgp.ernet.in.
authors.forename: Ranjit Prasad
authors.initials: RP
authors.lastname: Bahadur
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D030562:Databases, Protein; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D016601:RNA-Binding Proteins; D014867:Water; D012313:RNA