The inhibitory effect of a coronavirus spike protein fragment with ACE2.

Biophysical Journal
E. Peter, Alexander Schug

Abstract

In this article, we investigate the binding processes of a fragment of the coronavirus spike protein receptor binding domain (RBD), the hexapeptide YKYRYL on the angiotensin-converting enzyme 2 (ACE2) receptor, and its inhibitory effect on the binding and activation of the coronavirus-2 spike protein CoV-2 RBD at ACE2. In agreement with an experimental study, we find a high affinity of the hexapeptide to the binding interface between CoV-2 RBD and ACE2, which we investigate using 20 independent equilibrium molecular dynamics (MD) simulations over a total of 1 μs and a 200-ns enhanced correlation guided MD simulation. We then evaluate the effect of the hexapeptide on the assembly process of the CoV-2 RBD to ACE2 in long-time enhanced correlation guided MD simulations. In that set of simulations, we find that CoV-2 RBD does not bind to ACE2 with the binding motif shown in experiments, but it rotates because of an electrostatic repulsion and forms a hydrophobic interface with ACE2. Surprisingly, we observe that the hexapeptide binds to CoV-2 RBD, which has the effect that this protein only weakly attaches to ACE2 so that the activation of CoV-2 RBD might be inhibited in this case. Our results indicate that the hexapeptide might be...Continue Reading

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Citations

Aug 25, 2020·Tijdschrift voor economische en sociale geografie = Journal of economic and social geography = Revue de géographie économique et humaine = Zeitschrift für ökonomische und soziale Geographie = Revista de geografía económica y social·Annelies van Uden, Henk van Houtum
Dec 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Loai M SaadahIman A Basheti
Dec 16, 2020·Journal of Human Hypertension·Vivek BhallaAndrew M South
Mar 11, 2021·Biophysical Journal·Tamar SchlickM Madan Babu
May 19, 2021·Acta Pharmaceutica Sinica. B·Zinuo ChenQinghua Cui

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Methods Mentioned

BETA
NMR
x-ray crystallography

Software Mentioned

PRODIGY
GBSA
GROMACS
NPT
PyMOL
BLAST
CORE
MD
Basic Local Alignment Search Tool

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