Voltage-gating sodium ion channel structure modeling method based on development coupling analysis

Abstract

The invention relates to a voltage-gating sodium ion channel structure modeling method based on development coupling analysis, and belongs to the field of structural biology. The method includes the steps that through the rosetta membrane-protein homology modeling method, a eukaryon sodium ion channel NavPas (PDBid:5X0M) tertiary structure serves as a template, and four subunit structures of whicha Nav1.5 pore domain is composed are primarily established; through the development coupling analysis (DCA) method, the contact ratio between actual residue pairs and interaction residue pairs obtained after forecasting through DCA in the structures is evaluated; combined with a scoring function, the structures with the high score and the high contact ratio are selected as initiating structures of all structural domains; the four selected subunit structures are assembled and optimized; a structure capable of having the high interface contact ratio and the high RosettaMP score to meet the evaluation requirements is further selected from the optimized structures to serve as a final structure. According to the voltage-gating sodium ion channel structure modeling method based on development coupling analysis, the defects that in a traditional structure modeling method, transmembrane area information is not fully considered, the homology of a template is low, and the forecasting accuracy is poor are overcome, and the reliability is high.

Description

technical field [0001] The invention relates to a voltage-gated sodium ion channel structure modeling method based on evolutionary coupling analysis, which belongs to the field of structural biology, and in particular relates to eukaryotic voltage-gated sodium ion channel Na v 1.5 Structural modeling method targeting the closed state of the pore domain. Background technique [0002] Na v Channels are the source of neuronal initiation and propagation of action potentials, changing membrane potential through their rapid opening and closing. Na v The channel has three different functional states, in which the opening and closing of its pore domain (Pore domain) controls the selective passage of ions. At the same time, this domain is also an important binding region for many local anesthetic antiarrhythmic drugs. Many local anesthetic antiarrhythmic drugs are considered Na v Inhibitors of channels whose inhibitory effects are often enhanced by rapid, repeated stimulation or...

AI Technical Summary

Problems solved by technology

These methods perform better in protein structure prediction with a sequence length of less than 90, however, as the sequence length increases, the conformational search space grows exponentially, which is a great computational challenge

In this sense, the general problem of ab initio prediction of 3D structure remains unsolved

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