Protein-ligand binding free energy calculating method based on MM/PBSA model

Abstract

The invention provides a protein-ligand free energy calculating method based on a MM / PBSA model. The method comprises the following steps of respectively acquiring pdb files of a protein and a ligandmolecule; preprocessing the pdb file of the protein by means of a pdb4amber tool, deleting a hydrogen atom which cannot be read by Amber software; for the pdb file of the ligand molecule, converting the pdb format to a mol2 file format by means of an antechamber tool, and correcting the atom type to the atom type of an amber force field; assigning a GAFF force field parameter of the ligand molecule by means of a tleap command; respectively generating a topological file and a coordinate file of the protein, the ligand micromolecule and a protein-ligand micromolecule composite structure by meansof the tleap command through using an AMBER99SB-ILDN molecule force field parameter, and adding a water box and counter ions in the process; performing energy minimizing, heating and molecular dynamics simulation on a simulation system by means of the Amber software; and performing binding free energy calculation based on a molecular dynamics Poisson-Boltzmann surface area model on a molecular dynamics simulating track in a previous step by means of an MMPBSA.py program.

Description

technical field [0001] The invention relates to the technical field of molecular dynamics simulation, in particular to a protein-ligand binding free energy calculation method based on the MM / PBSA model. Background technique [0002] With the development of society and technology, great changes have taken place in treatment techniques. In addition to conventional surgery, radiotherapy, chemotherapy, biological therapy and traditional Chinese medicine treatment, pathogens have different targets at the organ, tissue and molecular levels. Targeted therapy can be performed using different targeted therapy techniques. [0003] At present, the commonly used targeted therapy technology includes targeted drug therapy technology. The key to targeted drug therapy technology is to study the interaction between proteins and ligand molecules. The combination of proteins and ligand molecules requires stereocomplementarity and chemical complementarity. Different ligand molecules show diff...

AI Technical Summary

Problems solved by technology

However, its calculation requires a large amount of computer consumption. In previous studies, only some structures selected from the database were theoretically calculated and verified. No researchers have yet performed high-throughput calculations.

[0006] In summary, the current general-purpose calculation method for binding free energy of proteins and ligand molecules still has problems such as large calculation errors and low calculation efficiency.

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