Function annotation of DNA repair related proteins using molecular evolution information and computer simulation of protein dynamics

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16570138
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biophysics
• Research Institution: Japan Atomic Energy Agency
• Principal Investigator: YURA Kei JAEA, CCSE, Senior Researcher, システム計算科学センター, 研究副主幹 (50252226)
• Co-Investigator(Kenkyū-buntansha): ISHIDA Hisashi JAEA, QuBS, Researcher, 量子ビーム応用研究部門, 研究職 (60360418) ; HIGUCHI Mariko JAEA, QuBS, Post Doctoral, 量子ビーム応用研究部門, 博士研究員 (90370460)
• Project Period (FY): 2004 – 2006
• Keywords: DNA repair protein / genome / database / MutT / RuvA / DNA photolyase / molecular evolution / molecular dynamics

Research Abstract

One of the hurdles that the field of genome biology is facing is to elucidate function of proteins deduced from genome nucleotide sequences. The best way to determine function of proteins is to carry out in vivo/in vitro experiments, yet the huge number of predicted proteins precludes performing whole types of experiments to each protein. Computational prediction of protein function can limit the necessary experiments to perform and can accelerate experimental function annotation. In this research, we have launched a project to identify functionally import amino acid residues in protein by computer simulation of protein dynamics and integrate the obtained data to the data of amino acid conservation gained by multiple sequence alignment of homologous proteins. Integration of both pieces of information was expected to improve the functional annotation of proteins. In this project we have succeeded in building database for DNA repair related proteins, improvement of functional annotation of MutT homologs (especially the ones derived from Deinococcus radiodurans), improvement of functional annotation of RuvA homologs, and improvement of functional annotation of DNA photolyase homologs. Especially in the case of DNA photolyase homologs, the correlation between the existence of functionally important residues identified by protein dynamics simulations and the conservation of amino acid residues was clearly observed. Protein dynamics simulations identified one amino acid residue crucial in an electron transfer pathway from FAD to damaged DNA. In the DNA photolyase homologs, the residues were almost completely conserved in proteins experimentally identified as DNA repair proteins, not completely mutated in proteins experimentally identified as non-DNA repair proteins. The residue was found to be a good maker for identifying DNA repair functions in DNA photolyase family (manuscript submitted).