Molecular virtual screening method based on protein sequence alignment

Abstract

The invention relates to a molecular virtual screening method based on protein sequence alignment, which comprises the following steps: according to an input protein sequence to be subjected to molecular screening, acquiring multi-sequence coupling information of protein by using an HHbits program; the frequency PSFM of the same residues appearing at the corresponding positions of the protein sequence to be predicted and the multi-sequence coupling information being calculated; by using the same method, generating the PSFM of each protein sequence in a protein-ligand interaction database BioLiP; calculating the residue alignment score and similarity matching quality of the to-be-predicted protein and each protein in BioLiP, and obtaining a potential seed molecule set according to the matching quality score; and calculating the sum of the two-dimensional fingerprint values of each molecule in the molecule database and all the molecules in the seed molecule set, sorting all the molecules in the DrugBank according to scores, and obtaining x.NDrugBank molecules with the top scores as a molecular sieve selection set of protein sequences to be subjected to molecular screening. The method can be used for any screening scene.

Description

technical field [0001] The invention relates to the fields of bioinformatics and computer applications, in particular to a molecular virtual screening method based on protein sequence alignment. Background technique [0002] Identifying lead molecules that interact with a given protein and appropriately modify its biological behavior is a fundamental challenge in pharmaceutical research. The virtual screening method uses molecular docking software on the computer to simulate the interaction between the target and the candidate drug, and calculates the affinity between the two, so as to reduce the number of actual screening compounds and improve the efficiency of lead compound discovery. Therefore, proposing a fast and accurate virtual screening method has important guiding significance for the design and development of drug molecules. [0003] Research literature found that many virtual screening methods have been proposed, such as: LncLocator (Cao Zhen, PanXiaoyong, Yang Y...

AI Technical Summary

Problems solved by technology

Although existing methods can be used for virtual screening of drug molecules, it is generally necessary to know the three-dimensional structure of a given protein or to know at least one binding molecule, so when there is no three-dimensional structure of the protein or the binding molecule is unknown, the existing Virtual screening methods don't work well

[0004] To sum up, the existing molecular virtual screening methods are still far from the requirements of practical applications in terms of screening scenarios and screening effects, and urgently need to be improved.

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