A structural topology-based method for predicting the three-dimensional structure of the transmembrane helix of G protein-coupled receptors

Abstract

The present invention provides a method for predicting the three-dimensional structure of the transmembrane helix of a G protein-coupled receptor based on structural topology, including: (1) constructing a structural topology model of the transmembrane helix: first constructing seven transmembrane helices of the G protein-coupled receptor (2) Predict the structural topology model of the transmembrane helix, which is divided into four stages: (21) The first stage is to identify the transmembrane helix region; (22) The second stage is to optimize the transmembrane helix region. The relative position between membrane helices; (23) The third stage is to optimize the rotation orientation of each helix in the membrane; (24) The fourth stage is to optimize the inclination angle of each helix and membrane; (3) Loop reconstruction: use Loop The fragments were inserted to link 7 helices, and finally the overall structure was slightly optimized. According to the spatial structure characteristics of the transmembrane helix, the method of the present invention establishes a structural topology model that takes into account both conservation and diversity, and uses the model to form a four-stage structure optimization method, trying to obtain a balance between sampling breadth and depth.

Description

technical field [0001] The invention relates to the technical field of G protein-coupled receptor structure prediction, in particular to a method for predicting the three-dimensional structure of the G protein-coupled receptor transmembrane helix based on structural topology. Background technique [0002] In 2012, two American scientists won the Nobel Prize in Chemistry for their outstanding research on G-protein-coupled receptors (GPCRs). The main significance of studying GPCR is that it is the largest superfamily of signal transduction proteins in the human body, which can interact with small molecules such as hormones, neurotransmitters, light, and odor molecules, and play an important role in cell signal transmission. The occurrence of major human diseases is often related to GPCR dysfunction. According to statistics, more than 10% of the world's top 200 best-selling drugs currently target GPCRs. GPCR is a special type of membrane protein embedded in biological membran...

AI Technical Summary

Problems solved by technology

The above-mentioned methods essentially encountered the same problem: it was difficult to achieve a balance between the conservation and local diversity of the seven transmembrane helical structures, and the essence was that the two were not unified into a system model

Images