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Review
. 2022 Sep;44(9):e2200060.
doi: 10.1002/bies.202200060. Epub 2022 Jul 17.

Molecular dynamics studies reveal structural and functional features of the SARS-CoV-2 spike protein

Ludovico Pipitò  1 , Roxana-Maria Rujan  1 , Christopher A Reynolds  1 , Giuseppe Deganutti  1
Affiliations
Review

Molecular dynamics studies reveal structural and functional features of the SARS-CoV-2 spike protein

Ludovico Pipitò et al. Bioessays. 2022 Sep.

Abstract

The SARS-CoV-2 virus is responsible for the COVID-19 pandemic the world experience since 2019. The protein responsible for the first steps of cell invasion, the spike protein, has probably received the most attention in light of its central role during infection. Computational approaches are among the tools employed by the scientific community in the enormous effort to study this new affliction. One of these methods, namely molecular dynamics (MD), has been used to characterize the function of the spike protein at the atomic level and unveil its structural features from a dynamic perspective. In this review, we focus on these main findings, including spike protein flexibility, rare S protein conformational changes, cryptic epitopes, the role of glycans, drug repurposing, and the effect of spike protein variants.

Keywords: SARS-Cov-2; drug repurposing; epitope; glycans; molecular dynamics; spike protein; variant.

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Conflict of interest statement

The authors do not have any conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
The S protein is the first promoter of SARS‐CoV‐2 internalization. (A) Overall architecture of the complex between S protein (prefusion conformation, cyan) and ACE2 (violet); glycans on S protein are in van der Waals spheres; the relative positions of the plasma and viral membranes are reported. (B) Magnification of the S1 ectodomain (glycans removed for clarity); the RBD in the up conformation is responsible for binding ACE2. (C) Magnification of the interface between the RBD and one of the ACE2 monomers; the interactions can be divided according to the relative position into sites 1 to 3 (red circles). (D) Fully glycosylated S protein (https://charmm‐gui.org/?doc=archive&lib=covid19) with the S1 and S2 units highlighted. The NTD, RBD, CTD, S1/S2 cleavage site, FP, HR1, HR2, TM, and CD are indicated. Glycans are shown in licorice. ACE2, angiotensin‐converting enzyme 2; CD, cytosolic domain; CTD, C‐terminal domain; FP, fusion peptide; HR, heptad repeat; NTD, N‐terminal domain; RBD, receptor‐binding domain; TM, transmembrane domain
FIGURE 2
FIGURE 2
S protein deposited structures in the protein data bank. (A) SARS‐CoV‐2 protein structures released and ordered according to month and year of publication from the Protein Data Bank[ 18 ] (B) S protein structures only, ordered according to resolution
FIGURE 3
FIGURE 3
Human antibodies can bind to different S protein epitopes. The binding position of five human Abs on the surface of the S protein, is colored according to the legend. Abs names and protein data bank database IDs are reported in the legend. The S protein is represented as a white surface, with the RBD in red. Abs, antibodies; RBD, receptor‐binding domain
See this image and copyright information in PMC

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