Conformational variability of loops in the SARS-CoV-2 spike protein

TL;DR

This study analyzes the conformational variability of loops in the SARS-CoV-2 spike protein, revealing that some loops exhibit multiple stable conformations, which impacts modeling accuracy and understanding of protein flexibility.

Contribution

It identifies and characterizes the conformational variability of spike protein loops and evaluates the challenges in modeling flexible regions based on structural data.

Findings

17 of 44 loops show multiple conformations

Loops with multiple conformations are harder to model

Most loops have a single stable conformation

Abstract

The SARS-CoV-2 spike (S) protein facilitates viral infection, and has been the focus of many structure determination efforts. Its flexible loop regions are known to be involved in protein binding and may adopt multiple conformations. This paper identifies the S protein loops and studies their conformational variability based on the available Protein Data Bank (PDB) structures. While most loops had essentially one stable conformation, 17 of 44 loop regions were observed to be structurally variable with multiple substantively distinct conformations based on a cluster analysis. Loop modeling methods were then applied to the S protein loop targets, and the prediction accuracies discussed in relation to the characteristics of the conformational clusters identified. Loops with multiple conformations were found to be challenging to model based on a single structural template.