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

作为基因组序列推断orf的功能预测方法，我们开发了一种将蛋白质模块的结构和功能特性转换为氨基酸序列模式的方法，称为“3D-keynote”。利用该方法，我们从蓝藻基因组中推断出ORF， slr0197的功能，并随后通过合作实验进行了验证。在此基础上，我们构建了一个自动生成各类功能3d主题的系统，完成了196种3d主题的生成，预测准确率平均在85%左右。将这些应用于蓝藻基因组，我们获得了推断大约12%功能未知的orf的功能的线索。3d主题也用于h -邀请赛的人类基因组注释（Yura & Go）。开发了糖-蛋白相互作用预测系统。严格和松散评价的预测精度分别为25%和66%，优于现有的其他方法。为了实验验证该预测系统，对凝集素等糖结合蛋白的晶体结构进行了分析。我们确定了六种新型复杂形式的凝聚蛋白的结构，并获得了支持该预测系统预测的糖结合位点存在的证据（Shirai）。疏水簇残基的链拓扑结构被发现是整个蛋白质分子链的简化表示。通过对疏水簇残基组成的伪肽链的分子动力学模拟和生成结构的聚类分析，我们将疏水簇残基的作用定义为它们的非特异性疏水聚集力使蛋白质链紧密，从而减少构象的搜索空间并加速折叠过程（Soda）。通过我们开发的鉴定备选剪接（AS）区域的方法，我们对人类全长cDNA数据进行了详尽的分析，我们发现大多数被AS改变的区域比蛋白质结构域的一般大小要短，这表明转录本的AS可能导致其蛋白质产物上的结构不稳定和/或相互作用位点的丢失，并导致所涉及的蛋白质网络途径的改变（Go & Takahashi）。少

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