Method for predicting binding free energy of protein and ligand based on progressive neural network

Abstract

The invention discloses a method for predicting the binding free energy of protein and ligand based on a progressive neural network, and belongs to the technical field of computer-aided drug design. The method comprises the steps: obtaining a pdb file from a PDBbind database, establishing local database, acquiring an amino acid molecule within 4.5 angstroms in the protein binding pocket by takingthe ligand molecule as a center, performing extended connectivity fingerprint calculation, carrying out SPLIF fingerprint calculation, searching for the number of salt bridges and hydrogen bonds between protein and ligand molecules, converting the structural information of the protein and the ligand into a one-dimensional tensor, and establishing a training set, a verification set and a test set;training the progressive neural network by using the training set; optimizing and searching hyper-parameters for prediction; through comparison with a molecular docking result, obtaining a higher Pearson correlation coefficient. According to the invention, the technical problem of how to convert a three-dimensional structure of protein and ligand molecules into tensors which are easy to calculateby a computer and input the tensors into the progressive neural network for training and optimization is solved, and the calculation rate and the prediction accuracy are greatly improved.

Description

technical field [0001] The invention belongs to the technical field of computer-aided drug design, and relates to a method for predicting the binding free energy of a protein and a ligand based on a progressive neural network. Background technique [0002] The free energy calculation method is related to the key field of drug design and is the core technology to realize high-throughput drug screening. The traditional experimental method based on random screening has problems such as long development cycle, high cost and blindness in the selection of massive drug molecules. How to screen tens of millions of molecules to obtain the final drug molecule is a problem that must be faced in drug screening. With the rapid development of computer technology and computational theoretical methods, a new drug development method, computer-aided drug design, has emerged. The method utilizes the fast calculation of the computer, combined with the physical model of the interaction between...

AI Technical Summary

Problems solved by technology

[0007] To sum up, the current general molecular docking method is not accurate enough, and the free energy calculation method based on physical models has time-consuming calculations and poor correlation of calculation results in the calculation of binding free energy between proteins and ligand molecules. question

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