Human 8-oxoguanine DNA glycosylase 1(hOGG1) plays a significant role of repairing oxidized genomic DNAs. The repair process includes the cleavage reaction of N-glycosidic linkage between 8-oxoguanine (8-oxoG) and the deoxyribose. To clarify the atomic-scale reaction mechanism of the N-glycosidic linkage cleavage, quantum chemical (QM) calculation at B3LYP/6-31G(d,p) was performed with a reaction model that consists of the catalytic Lys249 and guanosine that includes the 8-oxoG. It has been found from the QM calculation that the cleavage mechanism proceeds via three elementary reactions. In the first elementary reaction, a proton in the ammonium group of Lys249 is removed by the oxygen atom of 8-oxoG (8O) in concert with the generation of a new hydrogen bond between 8O and O4' of deoxyribose. In the second elementary reaction, N atom in Lys249 side chain (Nζ) nucleophilically attacks on C1' of the deoxyribose in concert with the spontaneous proton migration from 8O to O4'. The proton migration induces the dissociation of ether bond between O4' and C1'. Finally, a proton migrates from Nζ to N9 in 8-oxoG via 8O. N-glycosidic linkage between C1' and N9 is completely cloven in the final elementary reaction. It was confirmed that Schiff base appeared in products of the final reaction. According to the obtained base excision mechanism, 8O participates in the first and second elementary reactions. Therefore, this enzymatic reaction is a substrate-assisted catalysis. It was also found that the reaction path requires large activation energy (<42kcal/mol). This result finely reflects the experimental finding that the enzymatic activity of hOGG1 is not so high.

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We have developed molecular reactions that can be used for a DNA molecular memory. The DNA molecular memory is a memory based on DNA molecules and their molecular reactions. The DNA molecule is used as a memory element that has address information in its base sequence and the molecular reaction is used for memory addressing and data writing. Because of using molecules and molecular reactions, the memory is able to provide a large amount of memory space and allows a massively parallel addressing without physical wiring. Here, we report on the DNA molecules and molecular reactions that can be used for constructing the molecular memory.

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The distribution of net electric charge of amino acid sequences from Drosophila melanogaster is compared with a Gaussian distribution to investigate the balance between randomness and selection in the process of evolution. The net electric charge follows a Gaussian-like distribution, with a slight but systematic deviation from the Gaussian distribution. This deviation is not observed for eleven subsets of proteins of similar size, and it is shown that the mean and variance of the Gaussian distribution appear to be linearly dependent on the size of proteins. The Gaussian distribution is centered around a charge density of approximately one positive charge per 100 residues, which in comparison to the real distribution for random sequences, reveals some degree of charge correlation in the proteome of D. melanogaster. These findings suggest the possible involvement of a systematic selection mechanism in the evolution process.

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For the development of a high-performance software system of membrane protein prediction, we analyzed the distribution of hydrophobicity and the amphiphilicity around transmembrane helices, using dataset of membrane proteins whose 3D structures or topologies are known. The moving average of 7 residues showed that there are a hydrophobicity peak in the center of a transmembrane helix and two amphiphilicity peaks at both ends of the hydrophobicity peak. The shapes of the peaks were asymmetric with respect to the center of the hydrophobicity peak. The membrane protein prediction system SOSUI (Hirokawa and Mitaku, Bioinformatics, 1998) was improved on the basis of the asymmetric profiles of hydrophobicity and amphiphilicity, resulting in the accuracy of 98% for positive dataset and 96% for negative one of prokaryotes, and the comparable accuracy was obtained also for eukaryotes.

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