Cyclic peptide design method, compound structure generation method, device and electronic equipment

Abstract

The invention relates to a cyclic peptide design method, a compound structure generation method and device and electronic equipment. The design method comprises the following steps: acquiring an initial compound structure containing hot spot residues and target protein; adding amino acid along the N end and / or C end of the hot residue of the initial compound structure to obtain a linear peptide of which the length does not exceed a preset length threshold value, carrying out cyclopeptide conformation search according to the initial skeleton dihedral angle of the hot residue in the corresponding linear peptide, and screening to obtain candidate cyclopeptide conformations meeting preset cyclopeptide conditions; respectively optimizing each candidate cyclic peptide conformation and sequence to obtain a corresponding optimized cyclic peptide conformation and a cyclic peptide sequence corresponding to the optimized cyclic peptide conformation; and screening in the optimized cyclopeptide conformation, and determining a target cyclopeptide sequence of which the Pnear value is greater than a preset threshold value. According to the scheme provided by the invention, the cyclopeptide molecules capable of realizing targeted binding are designed from the beginning, so that the diversity of cyclopeptide conformation and cyclopeptide sequences is increased, and more reliable choices are provided for druggability of the cyclopeptide.

Description

technical field [0001] The present application relates to the technical field of cyclic peptide design, in particular to a method for designing cyclic peptides, a method for generating complex structures, devices and electronic equipment. Background technique [0002] Polypeptides are compounds between small molecules and proteins. Polypeptides also have a variety of structures, including chain polypeptides, cyclic peptides (that is, polypeptides with a ring structure), and so on. Since the chain-like peptides are too flexible, twisting and flipping at will, they are too loose to be good medicines. By introducing a ring structure, R&D personnel restrict the activity of the polypeptide, increase the stability of the polypeptide, make it exhibit better pharmacological activity and stability, and make it possible to make more polypeptides into drugs. [0003] In the cyclic peptide design scheme in the related art, excessive reliance on the hot spot residue fragments in the sec...

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Problems solved by technology

[0003] In the cyclic peptide design scheme in the related art, excessive reliance on the hot spot residue fragments in the secondary structure of the protein known to act on the target as the starting structure of the cyclic peptide design will constrain the conformational search space; in addition, only Consider the conformations associated with 20 natural amino acids, limiting the range of amino acid sequences that can form cyclic peptides

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