Novel medicament molecule construction method based on pharmacophore model

Abstract

The invention provides a brand new drug molecule construction method based on a pharmacophore model which relates to the medicine development assisted by computers. A pharmacodynamic characteristic segment is selected, folded and placed in an appropriate position in the pharmacophore model. The connection of the pharmacodynamic characteristic segment is controlled by a genetic algorithm to construct a new molecule completely fitting for the pharmacophore model. The method thereof comprises the following steps: the pharmacophore model is input; a sub-database of the pharmacodynamic characteristic segment and the connection is built; the pharmacodynamic characteristic segment is reasonably placed in the framework of the pharmacophore model, and the population is initialized; a judgment is made on whether the pharmacodynamic characteristic segment is directly connected or a linker is added; the produced molecule is judged on pharmacophore characteristic, space steric hindrance limitation and pharmacodynamic property; the individual fitness degree is calculated; with the operation of hybridization and mutation, and a new population is generated; a compositionality appreciation is carried out on a new compound produced. The method achieves the beginning design of the molecule under the condition that the three dimensional structure of the Danpabai is unknown, and the constructed molecule completely meets the requirement of the pharmacodynamic characteristic. The method is novel and has significant meaning.

Description

Technical field [0001] The invention relates to the field of computer-aided drug molecule design, in particular to a brand-new method for drug molecule construction using a pharmacophore model as initial information. Background technique [0002] According to the traditional drug development process, it takes at least 10 years to develop a new drug, and it is expensive. Not only that, but its success rate is also very low. In recent years, computer technology has been applied to drug research and development, and it is considered to be an effective means to shorten the new drug research and development cycle, reduce research and development costs and increase the success rate. [0003] The main way for computers to be used in drug development is computer-aided drug molecular design, and the design method based on the three-dimensional structure of target protein molecules is the most popular. Design methods based on the three-dimensional structure of target protein molecule...

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to solve the problem that the de novo design of drug molecules must rely on the complete knowledge of the three-dimensional structural information of the target protein molecule, otherwise it cannot be carried out, and at the same time overcome the defect that the newly designed compound is not easy to synthesize

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