Open AccessGeneralized Methodology for the Quick Prediction of Variant SARS-CoV-2 Spike Protein Binding Affinities with Human Angiotensin-Converting Enzyme II
Author(s) -
Alexander H. Williams,
Zhan Chen
Publication year - 2022
Publication title -
the journal of physical chemistry. b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 392
eISSN - 1520-6106
pISSN - 1520-5207
DOI - 10.1021/acs.jpcb.1c10718
Subject(s) - spike (software development) , affinities , spike protein , angiotensin converting enzyme 2 , binding affinities , chemistry , computational biology , covid-19 , biophysics , biology , biochemistry , computer science , medicine , receptor , software engineering , disease , pathology , infectious disease (medical specialty)
Variants of the SARS-CoV-2 virus continue to remain a threat 2 years from the beginning of the pandemic. As more variants arise, and the B.1.1.529 (Omicron) variant threatens to create another wave of infections, a method is needed to predict the binding affinity of the spike protein quickly and accurately with human angiotensin-converting enzyme II (ACE2). We present an accurate and convenient energy minimization/molecular mechanics Poisson-Boltzmann surface area methodology previously used with engineered ACE2 therapeutics to predict the binding affinity of the Omicron variant. Without any additional data from the variants discovered after the publication of our first model, the methodology can accurately predict the binding of the spike/ACE2 variant complexes. From this methodology, we predicted that the Omicron variant spike has a K d of ∼22.69 nM (which is very close to the experimental K d of 20.63 nM published during the review process of the current report) and that spike protein of the new "Stealth" Omicron variant (BA.2) will display a K d of ∼12.9 nM with the wild-type ACE2 protein. This methodology can be used with as-yet discovered variants, allowing for quick determinations regarding the variant's infectivity versus either the wild-type virus or its variants.