Compound property enhancement by virtual compound synthesis
| Autor: | Nobuaki Yasuo, Naoki Arai, Ryunosuke Yoshino, Masakazu Sekijima, Shunsuke Yoshikawa |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ofloxacin Computer science Property (programming) Ibuprofen 010402 general chemistry computer.software_genre 01 natural sciences Biochemistry Small Molecule Libraries 03 medical and health sciences chemistry.chemical_compound Molecular Biology Focus (computing) Drug discovery Anti-Inflammatory Agents Non-Steroidal Libraries Digital Computational Biology Chemical space 0104 chemical sciences Computer Science Applications 030104 developmental biology Web system chemistry Pharmaceutical Preparations Organic synthesis Data mining computer |
| Zdroj: | Journal of bioinformatics and computational biology. 16(3) |
| ISSN: | 1757-6334 |
| Popis: | During drug discovery, drug candidates are narrowed down over several steps to develop pharmaceutical products. The theoretical chemical space in such steps is estimated to be [Formula: see text]. To cover that space, extensive virtual compound libraries have been developed; however, the compilation of extensive libraries comes at large computational cost. Thus, to reduce the computational cost, researchers have constructed custom-made virtual compound libraries that focus on target diseases. In this study, we develop a system that generates virtual compound libraries from input compounds. When a user inputs a compound, the system recursively applies virtual synthetic reaction rules to the compound to improve its properties. The synthetic pathway can also be traced by the user because the reaction rules in this system are based on real organic synthesis reactions. This system has useful functions for effective drug design, such as structural preservation, allowing the substructures necessary for potency to be maintained. In this paper, to confirm the effect of directional reaction sets, we applied the reaction sets to 100 compounds. Moreover, to confirm that the system can reproduce real synthetic pathways, the synthetic pathways of Ibuprofen and Ofloxacin were explored by inputting isobutyl benzene and 7,8-difluoro-2,3-dihydro-3-methyl-4H-benzoxazine. This application is available at the following URL: http://enh.sekijima-lab.org . |
| Databáze: | OpenAIRE |
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