Method for performing de novo design of proteins without using templates

Abstract

The invention relates to a method for performing de novo design on part or all of protein. The method comprises the following steps: a, generating a main chain structure with high designability; and b, carrying out amino acid sequence selection and main chain correction iteration. According to the method, a main chain space structure of a to-be-designed protein can be generated by taking a pre-specified feature as a constraint condition, so that an amino acid sequence of the to-be-designed protein is determined, and the to-be-designed protein has the pre-specified feature; according to the method, when the to-be-designed protein main chain space structure is generated, a known specific protein local fragment does not need to be used as a structure template to splice and generate the to-be-designed protein structure, and a computer is used for optimizing a mathematical model (a statistical energy function model) obtained by learning from a large number of natural protein structures.

Description

technical field [0001] The invention belongs to the field of protein design, and in particular relates to a method for de novo design of part or all of the protein. This method can use the pre-specified features as constraints to generate the main chain space structure of the protein to be designed, and then determine the amino acid sequence of the protein to be designed, so that the protein to be designed has the pre-specified features; the method generates the space structure of the main chain of the protein to be designed At this time, it is not necessary to use known specific protein local fragments as structural templates to assemble the protein structure to be designed, but to use a computer to optimize the mathematical model (statistical energy function model) learned from a large number of natural protein structures. Background technique [0002] A variety of protein design methods exist in the prior art, but each has its own shortcomings. [0003] Automatic design ...

AI Technical Summary

Problems solved by technology

[0008] Since the fragment structure can only discretely represent the possible local structure space of polypeptides, the design results are limited by the resolution, accuracy, and completeness of the existing fragment collection, which makes the de novo protein structure design too single, too partial to ideal local structures, and lacks Due to the rich diversity of natural protein structures, it is impossible to fully search the designable main chain structure space in practical applications to obtain the optimal structure that meets the design requirements

Images