Interaction Analysis on the SARS-CoV-2 Spike Protein Receptor Binding Domain Using Visualization of the Interfacial Electrostatic Complementarity

Abstract

Visualization of the interfacial electrostatic complementarity (VIINEC) is a recently developed method for analyzing protein–protein interactions using electrostatic potential (ESP) calculated via the ab initio fragment molecular orbital method. In this Letter, the molecular interactions of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with human angiotensin-converting enzyme 2 (ACE2) and B38 neutralizing antibody were examined as an illustrative application of VIINEC. The results of VIINEC revealed that the E484 of RBD has a role in making a local electrostatic complementary with ACE2 at the protein–protein interface, while it causes a considerable repulsive electrostatic interaction. Furthermore, the calculated ESP map at the interface of the RBD/B38 complex was significantly different from that of the RBD/ACE2 complex, which is discussed herein in association with the mechanism of the specificity of the antibody binding to the target protein.

Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge-rule

“…refs. [23][24][25][26][27][28][29][30][31][32][33][34][35][36] ). Most of the studies have focused on the interactions involving the receptor-binding domain (RBD) of the SARS-CoV-2 spike homotrimer glycoprotein due to its biological central relevance.…”

Exploring the Spike-hACE 2 Residue–Residue Interaction in Human Coronaviruses SARS-CoV-2, SARS-CoV, and HCoV-NL63

“… 74 On the other hand, the mutation E484(K) leads to a small increase in the binding affinity of the complex, 75 and some computational studies have related it to a repulsive energy of E484, which is not present when the lysine residue is in position. 70 , 76 , 77 In our calculations, we only found one repulsion between E484 RBD and a hACE-2 residue ( Table S2 ), and it showed a quite small IE. This difference in the interaction energy could be related to the pose captured by the crystal structure, which represents a moment with favorable interactions, or to distinction in the calculation methods used.…”

“…These results are well correlated with previous experimental and computational data. 23 , 51 − 70 Spinello et al performed a multimicrosecond-long molecular dynamics simulations over the structures of SARS-CoV(−2)/ACE2 and SARS-CoV/ACE2 complexes, observing that regions of spike protein of SARS-CoV-2/ACE2 are markedly more rigid as compared to SARS-CoV, as well as they revealed a map of the most important H-bond and salt bridge interactions that enable it to be more stable. 51 Important studies using fragment molecular orbitals were carried out to characterize the protein–protein interactions (PPI) between RBD and several antibody/peptides 52 as well as PPI in the RBD-hACE2 interfaces.…”

Adsorption of Pulmonary and Exogeneous Surfactants on SARS-CoV-2 Spike Protein

“…The observed ability of surfactants to be adsorbed on cationic residues presents a special interest, as the overall cationic character of S1 domain with a net charge of +5 is the driving force for the Spike protein binding to highly negatively charged ACE2 protein. 25…”

“…The observed ability of surfactants to be adsorbed on cationic residues presents a special interest, as the overall cationic character of S1 domain with a net charge of +5 is the driving force for the Spike protein binding to highly negatively charged ACE2 protein. 25 Understanding the surfactant affinities of various amino acid residues shown in Figure 4 helps to predict the behavior of the CoV-2 variants. S1 domain is strongly cationic with ARG and LYS being preferential sites for surfactant adsorption.…”