title: Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling.
abstract: With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Ramachandra M
authors.initials: RM
authors.lastname: Bhaskara
authors.forename: Amrita
authors.initials: A
authors.lastname: Padhi
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Srinivasan
mesh_terms: D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012372:ROC Curve
chemical_list: D011506:Proteins
keywords: difference domain architecture; differential residue conservation; interface evolution; knowledge-based docking; naïve Bayesian classifier