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Updated: Jan 18, 2026

High Precision FRET at Single-molecule Level for Biomolecule Structure Determination
Published on: May 13, 2017
Molecular determinants for ligand binding at Nav1.4 and Nav1.7 channels: Experimental affinity results analyzed by
De-Jiang Kong1, Ying Wang1, Han-Xun Wang1
1Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Abstract:
Here, we focused on exploring the selectivity mechanism against Nav1.7 over Nav1.4 due to different binding modes of two selected inhibitors. By the superposition of Nav1.7 and Nav1.4 proteins, we selected the most homologous chain of Nav1.7 with Nav1.4, defining the active site of Nav1.4-VSD4 based on the aryl sulfonamide binding site of Nav1.7-VSD4. Comparison of the conformations exhibited by Tyr1386 (Nav1.4) and Tyr1537 (Nav1.7) suggested that the steric hindrance caused by Tyr1386 owned primary influence on inhibition selectivity, which was further verified through molecular docking and MD simulation of two representative inhibitors. Our finding would be helpful for discovery of selective Nav1.7 inhibitors over Nav1.4.
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