Method and system for simulating ligand molecule and target receptor reaction and calculating and forecasting thermodynamics and kinetics parameters of reaction

Abstract

The invention relates to a method and application system for simulating ligand molecule and target receptor reaction based on a computer and calculating and forecasting thermodynamics and kinetics parameters of the reaction. The method mainly comprises the following steps of: designing a method for calculating combined free energy of a ligand molecule and a target receptor, and designing a multi-target molecule docking method and developing an application system of the docking method based on the calculating method; simulating and sampling the interaction mode of the ligand molecule and the target receptor by the system, grading the free energy combination of the ligand molecule and the target receptor, and building a method and system for the potential energy surface of the combined free energy of the ligand molecule and the target receptor according to the simulating and sampling result; building a method and system for identifying a reaction path of the ligand molecule and the target receptor according to the potential energy surface; and determining a active site and a transition site of the reaction to calculate the thermodynamics and kinetics parameters. The method and the system provide important basis and a forecast evaluation method for drug development, and are expected to improve the drug development efficiency and save experimental expenses greatly, thus serving as an effective auxiliary means for the drug development.

Description

technical field [0001] The invention belongs to the fields of medicine, computational chemistry, computational biology and drug design, and relates to a computer-based simulation of the reaction between a ligand molecule (for example, a drug molecule) and a target receptor (such as a protein, nucleic acid, and other disease targets), and obtains the A new approach to thermodynamic and kinetic parameters of reactions. The method can accurately simulate the interaction mode and reaction (binding / dissociation) mode of the ligand molecule and the target receptor at the molecular level, and quickly and accurately calculate and obtain the thermodynamic and kinetic parameters of the reaction, and obtain the ligand molecule and target receptor. The binding or dissociation path of the target receptor reaction, and then discover the key interaction sites (active site and transition state site) of the target receptor-ligand molecule, which is suitable for quantitative and qualitative ana...

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Problems solved by technology

[0007] The technical problem to be solved in the present invention is to simulate the interaction mode between the ligand molecule and the target receptor, obtain the reaction mode between the ligand molecule and the target receptor (binding or dissociation), and calculate the thermodynamic parameters and kinetic parameters of the reaction , determine the key binding sites experienced by the ligand molecule when it reacts with the target receptor, and then guide the design or transformation of the drug molecule, while overcoming the time-consuming and inaccurate defects of the simulation calculation method in the prior art, improving the efficiency of drug development and reducing the R&D cost

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