The Role of Spike Protein Mutations in the Infectious Power of SARS‐COV‐2 Variants: A Molecular Interaction Perspective

Abstract

Specific S477N, N501Y, K417N, K417T, E484K mutations in the receptor binding domain (RBD) of the spike protein in the wild type SARS‐COV‐2 virus have resulted, among others, in the following variants: B.1.160 (20A or EU2, first reported in continental Europe), B1.1.7 (α or 20I501Y.V1, first reported in the United Kingdom), B.1.351 (β or 20H/501Y.V2, first reported in South Africa), B.1.1.28.1 (γ or P.1 or 20J/501Y.V3, first reported in Brazil), and B.1.1.28.2 (ζ, or P.2 or 20B/S484K, also first reported in Brazil). From the analysis of a set of bonding descriptors firmly rooted in the formalism of quantum mechanics, including Natural Bond Orbitals (NBO), Quantum Theory of Atoms In Molecules (QTAIM) and highly correlated energies within the Domain Based Local Pair Natural Orbital Coupled Cluster Method (DLPNO‐CCSD(T)), and from a set of computed electronic spectral patterns with environmental effects, we show that the new variants improve their ability to recognize available sites to either hydrogen bond or to form salt bridges with residues in the ACE2 receptor of the host cells. This results in significantly improved initial virus⋅⋅⋅cell molecular recognition and attachment at the microscopic level, which trigger the infectious cycle.

Ring Vibrations to Sense Anionic Ibuprofen in Aqueous Solution as Revealed by Resonance Raman

“…(2) d→a energy values, calculated for the interactions in that snapshot, are in the same ranges as those found in a-Ibu/water clusters coming from exhaustive explorations of the PESs, reinforcing the fact that randomly choosing configurations from classical mechanics simulations are reliable sources to gain deep insight about inter-fragment bonding, a strategy that has been recently used in several works [10,[77][78][79][80].…”

Perspective Chapter: Bioinformatics Study of the Evolution of SARS-CoV-2 Spike Protein

“…In the ACE2 PPI, however the following mutations are present with calculated FoldX Δ energies in kcal/mol: K417N: −0.34, G446S: 2.99, N440K: −0.61, S477N: 0.14, T478K: −0.18, E484A: 1.31, Q493K: −1.20, G496S: −0.06, Q498R: −0.93, N501Y: 6.18 and Y505H: 1.62. The results confirm the observed ensemble of mutations substantially modify the resulting PPI in accordance with the literature [52][53][54][55][56][57][58][59][60]. It should be stressed, that FoldX evaluations are single-point only and detailed binding energetics should be further studied by experiment supported MD.…”

Analysis of Conformational Preferences in Caffeine

“…Thus, QTAIM suggests a wrong conformation for M3 favoring the 1,4-allylic effect over the C-H/C-H eclipsing and even over the 1,3-allylic effect while saying nothing about the conformational preferences of M1 and M2. The very small accumulation of electron density at the bond critical points, a. u., about half that of the water dimer [ 43 , 44 ], a well studied weakly bonded system, is a good descriptor of the tiny rotational barriers. NCI affords green (with a small amount of red) surfaces for all conformations of M1 and M2, and only for the M3 conformation which eclipses a carbonyl group ( Figure 2 ).…”

“…In this scenario, honoring Frank Weinhold on occasion of his 80th birthday, we resort to NBO and other analysis methods to resolve this structural conundrum. NBO, developed over the last few decades in the group of Frank Weinhold [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], is a widely used and highly successful strategy in the analysis of a large body of chemical problems [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Specifically, for the conformational problem in caffeine, for each methyl rotation, we study hyperconjugation, electron delocalization involving the methyl groups, NBO donor–acceptor interactions, and the effect of all these factors on geometrical variables.…”