What is it about?
- Is the center-of-mass (CoM) distance a reliable method to estimate the binding affinity impact of induced mutation(s) in heterodimeric proteins? - Which limitation has usually been overlooked? - How it can be solved? - Which Gromacs commands should be applied? - In silico experiment to estimate the binding affinity impact of K417Y SARS-CoV-2 S-protein mutation. - Detailed analysis of the intermolecular interactions involving K(Y)417 residues.
Featured Image
Photo by National Cancer Institute on Unsplash
Why is it important?
- Neglect prior-convergent proteins' dynamics and focus on the convergent phase only. - Measure and compare the convergent CoM distance between monomers in heterodimers! - that will give you accurate insights of the binding affinity impact of induced mutation(s). - Method's application proved reduced binding affinity in S-protein - hACE2 complex due to K417Y SARS-CoV-2 mutation. - The finding was derived based on analysis of the convergent CoM distance between monomers in K417 (wild type) and Y417(mutant) heterodimeric proteins. - Validity of findings also approved by detailed analysis of the intermolecular contacts: types and occupancy.
Perspectives
K417Y mutation in SARS-CoV-2 S-protein, shifts the permanent salt bridge (occupancy: 98.5%), formed between deprotonated carboxylic acid COO− in D30 (aspartic acid, hACE2) and the positively charged ε-amino group NH3+ in K417 (Lysine, S-protein) into a hydrogen bond of temporary character (occupancy: 24.8%), formed between D30 carboxylate ion and Y417 phenolic hydroxyl group (-OH), that contributes towards reduced binding affinity between the SARS-CoV-2 S-protein and hACE2 receptor.
Ph.D Done Stojanov
Univerzitet Goce Delcev Stip
Read the Original
This page is a summary of: On the in silico application of the center-of-mass distance method, Gene & Protein in Disease, March 2024, Inno Science Press,
DOI: 10.36922/gpd.2657.
You can read the full text:
Contributors
The following have contributed to this page
