1988 Fiscal Year Final Research Report Summary
Development of computer drug design softwares for purpose of lead generation
| Project/Area Number |
62870090
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Teikyo University (1988)
The University of Tokyo (1987) |
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Principal Investigator |
IITAKA Yoichi Department of Medicine, Teikyou University, 医学部, 教授 (90012591)
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| Co-Investigator(Kenkyū-buntansha) |
ITAI Akiko Faculty of Pharmaceutical Sciences, University of Tokyo, 薬学部, 助手 (60012647)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Computer drug design / lead generation / 構造活性相関 / コンピュータ・プログラム |
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| Research Abstract |
Successful results of protein crystallography gave us concrete and minute image of molecular recognition by biological macromolecules, or of drug-receptor interactions. Computer simulations of molecular interactions, stabilities, chemical reactivities as well as physical properties are useful for designing new active structures. But, these techiques are not efficient for generating active molecules with new skeletal structures.
The aim of this research is to develop new methods and softwares of the computer drug design for the purpose of lead generation. We have developed two program systems on the basis of drug-receptor theory. In the case of three-dimensional structures of receptors (or target macromolecules) is known: simulate the linding of drugs to the receptor. Various data calculated at each three-dimensional grid point inside the drug binding site of receptor whick exhibit the local physical and chemical character of the linding site, are used for estimating the interaction energy between drug and receptor in realtime. This method facilitates the evaluation of the structure-activity relationships and mechanisms of biological reactions, and construct ion of new structures which can well fit to the binding site.
In the case of the receptor structure is unknown: superpose the drug molecules by estimating physical and chemical characters at each three-dimensional grid point, and construct a receptor model on the basis of superposed structures. This method enables to explain the relationships between structures and activities among molecules with similar activities but quite different chemical structrues.
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