Decoding of genome function and evolution based on the 3D structures of proteins

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As a functional prediction method for ORFs inferred in genome sequences, we developed a method to convert structural and functional properties of protein modules into amino acid sequence patterns, called "3D-keynote". Using the method, we inferred a function of ORF, slr0197 from a cyanobacterium genome, which was subsequently verified by collaborative experiments. Furthermore, we made an automatic system to generate 3D-keynotes for each kind of functions and accomplished generations of 196 kinds of 3D-keynotes, whose prediction accuracies were evaluated to be about 85% on an average. Applying these to a cyanobacterium genome, we obtained clues for inferring the functions for about 12% of function-unknown ORFs. The 3D-keynotes were also used for human genome annotation in H-invitational (Yura ＆ Go).A sugar-protein interaction prediction system was developed. Strict and loose evaluations of the prediction accuracy resulted in 25 and 66%, respectively, which were better than other existin … More g methods. To experimentally verify the prediction system, crystal structure analyses of sugar-binding proteins such as lectin, were done. We determined structures of six novel complex forms of congerin and obtained evidences supporting the existence of sugar-binding sites predicted by the prediction system (Shirai).A chain topology of hydrophobic cluster residues was found to be a reduced representation of a whole chain of the protein molecule. From molecular dynamics simulations of a pseudo-peptide chain composed of hydrophobic cluster residues and cluster analyses of the generated structures, we defined roles of hydrophobic cluster residues as their non-specific hydrophobic aggregation forces made the protein chain compact to decrease the search space for conformations and accelerate the folding process (Soda).Exhaustively analyzing human full-length cDNA data by the method we developed to identify alternative splicing (AS) regions, we found that most regions altered by AS were shorter than common sizes of protein domains, and indicated possibilities that AS of transcripts may lead to structural destabilization of and/or loss of interaction sites on their protein products and result in changing pathways of the protein network involved (Go ＆ Takahashi). Less