Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation

Abstract

Many key residues, which mediate the interaction between SARS-CoV2 spike glycoprotein (S protein) and human ACE2 receptor, have been reviewed using the SARS-CoV2 S spike protein with human ACE2 complex. The initial SARS-CoV2 S protein and ACE2 protein complex structure is formed by RBD structure of SARS-CoV2 S protein and ACE2 protein. However, the cryo-EM structure study targeting SARS-Cov S protein with human ACE2 complex has shown that there exist different binding conformations during the binding process facing ACE2 protein. It suggests the interaction between SARS-CoV2 S spike protein complex might have different binding conformations, which request full-length of SARS-CoV2 S protein complex in the structure-functional analysis. In this study, we built a full-length SARS-CoV2 S protein with human ACE2 complex by computational methods. Residues K31, H34, E35 in ACE2 protein were showed both in our full-length model and RBD structure model, which recognized as critical residues in previous studies. Surprisingly, ACE2 residues E564, R559, N556 were only found participating in the interaction of our full-length model, which suggested the full-length model has bigger binding interface. This finding was further supported by the interaction network of full-length model and RBD model. Meanwhile, the method bias was taken into consideration. Eventually, the MM-PBSA results showed the full-length model had a stronger binding free energy (almost 5-fold) than the RBD structure model of SARS-CoV2 S spike protein complex. In computational level, we present a stronger binding model containing a full-length structure of SARS-CoV2 S protein with ACE2 complex.

Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies

“…1 ). Several theoretical works on the RBD interface can be found in the bibliography, mainly addressing S/ACE2 interactions, although the theoretical works with the CR3022 and S309 mAbs are scarce [ [27] , [28] , [29] , [30] , [31] ]. Most of these works present a classic approach to the interactions either from classical molecular dynamics (cMD) point of view or using docking methodologies.…”

Artificial Lipid Biomembranes for Full‐Length SARS‐CoV‐2 Receptor

“…However, full‐length ACE2 models may generate larger interaction networks with RBD and more binding interfaces. [ 42 ] Undoubtedly, a change in the free binding energy may have affected the conformational change of the S protein, thus affecting the binding of ACE2 to RBD. Therefore, full‐length ACE2 can provide more accurate information for exploring its structure and function.…”

SARS-CoV-2 induces transcription of human endogenous retrovirus RNA followed by type W envelope protein expression in human lymphoid cells.

“…This activation was also obtained with a recombinant trimer tested for an effective binding to ACE2 receptors, but not stabilized in a speci c conformation. Pre-and post-fusion variable conformations of this spike protein may confer divergent properties 52 , whereas vaccine preparations are likely to stabilize its structure [53][54][55] with a good safety pro le 54,56 . Here again, further studies are needed to de ne sequence-related and protein conformational properties involved in a proteinreceptor interaction leading to HERV activation in susceptible individuals.…”