Unlock instant, AI-driven research and patent intelligence for your innovation.

Protein skeleton design method and application thereof

A design method and protein technology, applied in the biological field, can solve the problems of low efficiency, uneven quality of protein structure models, a large number of manual inspections, etc., and achieve the effect of high efficiency and high sequence designability

Active Publication Date: 2021-02-19
北京晶泰科技有限公司
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Existing skeleton generation methods are inefficient, and the quality of the obtained protein structure models is uneven, requiring a lot of manual inspection and parameter evaluation, filtering the database, time-consuming and laborious, and human visual inspection standards cannot be unified

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Protein skeleton design method and application thereof
  • Protein skeleton design method and application thereof
  • Protein skeleton design method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Design of Small Protein Skeleton and Its Amino Acid Sequence Using Improved Method

[0047] 1) Prepare a small protein-specific HLH fragment database

[0048] In order to improve the HLH fragment assembly efficiency of the SEWING calculation method, the database information in the original method has been adjusted. The original database uses the length of each helix in the HLH fragment to be 5-40 amino acids, which is not suitable for designing small proteins. skeleton. The improved method is to extract non-redundant data with resolution accuracy below 3.0 Å and 30% sequence similarity from the PDB database as the input set of data, and separate HLH fragments with each helical length of 5-25 amino acids. A new database was prepared to control the size of the helical structure within the range of 30-90 amino acids.

[0049] 2) Use the improved SEWING method to generate small protein backbones

[0050] The HLH fragment structure assembled in the SEWING genera...

Embodiment 2

[0066] Example 2 Using a stable small protein backbone structure to design targeted binding drugs

[0067] 1) Isolation of key interacting structural motif fragments from crystal structures.

[0068] Step 1.1: Search the structure of the target protein in the PDB database. If there is a high-precision crystal structure, download its PDB file, and remove irrelevant molecular information such as water molecules, ions, substrates, etc., using the default Rosetta Relax program parameters to optimize the protein structure.

[0069] Step 1.2: Use the Rosetta ddG Mover program to calculate the binding free energy change of the crystal complex structure and scan all residue sites on the interaction interface, and set the amino acids whose free energy contribution is greater than 0.5 REU energy units as hotspot residues . The continuous secondary structures connecting these hotspot residues and the structure of the target were isolated and saved as a new PDB structure.

[0070] 2) M...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a design method and application of a small protein skeleton, and the design method comprises the following steps: S1, creating a special structural fragment database; s2, generating a small protein skeleton database; s3, performing amino acid sequence optimization and design on a small protein skeleton; and S4, evaluating and filtering the structure by adopting indexes related to the stability, removing and filtering the structure which does not meet the standard, and finally forming the small protein which can be stably folded in calculation and prediction. The biggestdifference between the method and an existing method lies in that a topological structure reported and designed in literature is HLHLHLHLH, a smaller protein of which the topological structure is HLHLHLH is designed, a stricter filtering standard is specially defined according to the HLHLH topological structure, and an SEWING sampling method is improved. Therefore, the stability and sequence designability of the designed protein should be higher, and the generation efficiency of a high-quality skeleton in the calculation process is higher.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a protein skeleton calculation design method and its application. Background technique [0002] Currently, random assembly of protein fragments from crystal structures or secondary structural units from crystal structures is used to generate protein structures and sequences with specific folding patterns. Existing skeleton generation methods are inefficient, and the quality of the obtained protein structure models is uneven, requiring a lot of manual inspection and parameter evaluation, filtering the database, time-consuming and laborious, and human visual inspection standards cannot be unified. And when designing small proteins for targeted binding, there are often no suitable small protein backbone templates, so it is necessary to increase the available small protein backbone data. Contents of the invention [0003] Therefore, the present invention provides an improv...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): G16B5/00G16B30/10G16B30/20G16B40/00G16B50/00
CPCG16B5/00G16B30/10G16B30/20G16B40/00G16B50/00Y02A90/10
Inventor 王天元吴炜坤赖力鹏温书豪马健
Owner 北京晶泰科技有限公司