Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: Implications for three-dimensional modeling

作者：Bhaskara Ramachandra M; Padhi Amrita; Srinivasan Narayanaswamy^*

来源：Proteins: Structure, Function, and Genetics , 2014, 82(7): 1219-1234.

DOI：10.1002/prot.24486

• interface evolution
• difference domain architecture
• differential residue conservation
• naive Bayesian classifier
• knowledge-based docking

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 naive Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (approximate to 85%) and specific (approximate to 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. Proteins 2014; 82:1219-1234.

• 出版日期2014-7