Free-energy landscape of molecular interactions between endothelin 1 and human endothelin type B receptor: fly-casting mechanism.

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2019
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Abstract
The free-energy landscape of interaction between a medium-sized peptide, endothelin 1 (ET1), and its receptor, human endothelin type B receptor (hETB), was computed using multidimensional virtual-system coupled molecular dynamics, which controls the system's motions by introducing multiple reaction coordinates. The hETB embedded in lipid bilayer was immersed in explicit solvent. All molecules were expressed as all-atom models. The resultant free-energy landscape had five ranges with decreasing ET1-hETB distance: completely dissociative, outside-gate, gate, binding pocket, and genuine-bound ranges. In the completely dissociative range, no ET1-hETB interaction appeared. In the outside-gate range, an ET1-hETB attractive interaction was the fly-casting mechanism. In the gate range, the ET1 orientational variety decreased rapidly. In the binding pocket range, ET1 was in a narrow pathway with a steep free-energy slope. In the genuine-bound range, ET1 was in a stable free-energy basin. A G-protein-coupled receptor (GPCR) might capture its ligand from a distant place.
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higo2019freeenergyprotein Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Higo, Junichi;Kasahara, Kota;Wada, Mitsuhito;Dasgupta, Bhaskar;Kamiya, Narutoshi;Hayami, Tomonori;Fukuda, Ikuo;Fukunishi, Yoshifumi;Nakamura, Haruki;
Journal protein engineering, design & selection : peds
Year 2019
DOI
gzz029
URL
Keywords
molecular dynamics gpcr enhanced sampling generalized ensemble membrane protein molecular docking potential of mean force

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