2017 Fiscal Year Final Research Report
Development of in silico fragment-based drug design method for rational drug discovery
| Project/Area Number |
15K07899
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAOTSU Noriyuki 北里大学, 薬学部, 講師 (60230322)
NAKAGOME Izumi 北里大学, 薬学部, 助教 (30237242)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | in silico 創薬手法 / フラグメントマッピング法 / SBDD / FBDD |
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| Outline of Final Research Achievements |
Here, we propose an in silico fragment-mapping method as a potential tool for Fragment-based drug discovery (FBDD). For this method, we created a database named Canonical Subsite-Fragment DataBase (CSFDB) and developed a knowledge-based fragment-mapping program, Fsubsite. CSFDB consists of various pairs of subsite-fragment derived from X-ray crystal structures of known protein-ligand complexes. Using three-dimensional similarity-matching between subsites on one protein and another, Fsubsite compares the surface of a target protein with subsites in CSFDB. When a local topography similar to the subsite is found on the surface, Fsubsite places a fragment combined with the subsite in CSFDB on the target protein. When all subsites in CSFDS are examined, the fragment-mapping onto the target protein is completed. As a result of several validations of the method, we are sure that the in silico fragment-mapping method is a useful tool for computational structure-based drug design and FBDD.
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| Free Research Field |
計算化学・物理化学・医薬分子設計
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