Free-energy landscape of molecular interactions between endothelin 1 and human endothelin type B receptor: fly-casting mechanism
Year: 2019
Type: article
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.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,656
Awards: kinetic constants of molecular binding calculated from equilibrium, G3291055677, G3700386206, Computational design of novel proteins with weak interactions, G5219178975, Computational study for multistery of intrinsic disordered region of proteins with post-translational modification, G7907785530, G893167776
OpenAlex ID: W2980985309