Two Achilles' Heels of the Ebolavirus Glycoprotein?

Abstract

Ebolavirus has a membrane envelope decorated by trimers of a glycoprotein (GP), which is responsible for host cell attachment and membrane fusion. Therefore, GP is a primary target for antiviral drugs development. Here, this article reports the first, to my knowledge, set of structural analysis of all Ebolavirus GP structures as of March 10, 2020, and also a brief update of the structurally identified electrostatic features of the Ebolavirus GP structures in both apo (unliganded) state and also in bound states with a series of small compounds, including a variety of approved drugs. With this comprehensive set of structural analysis, this article puts forward a hypothesis of two Achilles' heels of Ebolavirus GP structure, where the formation of two interfacial salt bridges, instead of destabilizing the prefusion conformation of Ebolavirus GP, constitutes a positive contribution towards the structural rigidification of the prefusion conformation of the Ebolavirus GP structure, thereby acting against GP-mediated Ebolavirus cell entry and/or preventing fusion between the viral and endosome membranes.

A Reversible Spherical Geometric Conversion of Protein Backbone Structure Coordinate Matrix to Three Independent Vectors of ρ, θ and φ

“…Therefore, in this manuscript, I put forward an inter-atomic spherical coordinate system (IASCS) approach to redefine protein structure with ρ, θ and ϕ [89] for the reversible spherical geometric conversion of protein backbone structure coordinate matrices into three independent vectors: ρ, θ, and ϕ. Unlike traditional Cartesian coordinates, which represent a protein's backbone geometry in terms of its x, y, and z coordinates, the approach here leverages spherical coordinates to capture the inherent curvature (i.e., structural features [90]) of protein backbone structures more intuitively. By transforming the Cartesian coordinate matrix into spherical coordinates, this approach effectively decouple the spatial information into radial distance (ρ), polar angle (θ), and azimuthal angle (ϕ), providing a more natural representation of the protein's backbone conformation [91].…”

Ab Initio Modelling the Structure of Proton-Sensing G-Protein Coupled Receptor GPR151

“…It has been almost half a century since the launch of Protein Data Bank (PDB) in 1971 [1]. Biophysical tools such as X-ray crystallography, NMR spectroscopy and Cryo-electron microscopy have contributed enormously to the continued development of PDB [2], with which a variety of computational tools have been developed for biomolecular structural modelling, classification and feature extraction [3][4][5][6][7][8][9][10][11][12] and functional prediction. For instance, ab initio protein structural modelling [13,14] is an energy function-guided method to predict protein structure in the absence of experimentally solved structure of a similar/homologous protein.…”