What is it about?
Following study main findings, N501Y SARS-CoV-2 mutation implies conformational destabilization upon SARS-CoV-2 S. Protein Receptor Binding Domian that actually leads to intensified intermolecular polar interactions between the virus and hACE2 receptor. The present study provides completely novel biomolecular findings for better understating of the key aspects of the controversial N501Y mutation.
Featured Image
Photo by Jan Kopřiva on Unsplash
Why is it important?
Main findings: 1. The N501Y mutation shifts the Gly502 N-H…O=C Lys353 intermolecular hydrogen bond into a permanent polar interaction, which is of temporary character in the wild type N501. 1.1. Energy calculations: E(Gly502 N-H…O=C Lys353) in N501Y=4.816210332kcal/mol E(Gly502 N-H…O=C Lys353) in N501=3.909532232kcal/mol 2. Enhanced electrostatic interaction between Tyr505 (RBD) phenolic -OH group and Glu37 (hACE2) side chain oxygen atoms due to the N501Y mutation. 3. The N501Y mutation shifts α-helix S-protein RBD [366-370]: SerValLeuTyrAsn into π-helix. 4. An S-protein RBD [503-505]: ValGlyTyr shift from 3/10-helix into a turn is observed due to the N501Y mutation. 5. An empirical proof for the presence of a Y501-binding pocket, based on RBD [499-505]: PTYGVGY Cα’s RMSF peak formation is presented.
Perspectives
Despite of the well-documented findings for Y501-K353 π-cation interaction and Y501…Y41 π-π stacking interaction that result in increased binding affinity due to the formation of the Y501-binding pocket, the present study reveals that the binding affinity is additionally increased by formation of a permanent and stronger G502-K353 hydrogen bond in the presence of Y501. Following the findings from the present study, Y501 also intensifies the Y505-E37 polar interaction. The present study has also found that two stable RBD α-helices are destabilized into a π-helix and turn respectively in the presence of Y501. Finally, an empirical proof for the presence of the Y501-binding pocket was presented, estimated by means of Cα’s RMSF RBD [499-505]: PTYGVGY peak formation, which is adjacent to the hACE2 Y41 binding interface.
Ph.D Done Stojanov
Univerzitet Goce Delcev Stip
Read the Original
This page is a summary of: Structural implications of SARS-CoV-2 Surface Glycoprotein N501Y mutation within receptor-binding domain [499-505] – computational analysis of the most frequent Asn501 polar uncharged amino acid mutations, Biotechnology & Biotechnological Equipment, May 2023, Taylor & Francis,
DOI: 10.1080/13102818.2023.2206492.
You can read the full text:
Contributors
The following have contributed to this page
