Fragment molecular orbital based interaction analyses on complexes between SARS-CoV-2 RBD variants and ACE2

Abstract

The SARS-CoV-2 virus initiates infection of human cells by recognizing the human angiotensin-converting enzyme 2 (ACE2) with the receptor binding domain (RBD) of the viral spike protein. Thus, the variant of concern (VOC) with mutations on RBD is of special interest. Here, we present a series of interaction analyses for the RBD–ACE2 complex of the wild-type (PDB ID: 6M0J) and those of B.1.1.7 (α), B.1.351 (β) and P.1 (γ) VOCs, based on the fragment molecular orbital (FMO) calculations. The results revealed that the RBD variants have a higher affinity for ACE2 than the wild type does.

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

“…These results are well correlated with previous experimental and computational data. ,− 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 . Important studies using fragment molecular orbitals were carried out to characterize the protein–protein interactions (PPI) between RBD and several antibody/peptides as well as PPI in the RBD-hACE2 interfaces .…”

“…It is important to mention that mutations in spike residues K417­(N/T), E484­(K), and N501­(Y) have been found in some SARS-2 variants, possibly involved in reducing neutralization by some antibodies. ,,,, From these, N501Y is present in lineages B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), and E484K was observed in lineages Beta and Gamma, which also possess alternative amino-acid substitutions K417N and K417T, respectively. Watanabe et al, using the fragment molecular orbital method, found the K417N/T, E484K, and N501Y mutations are energetically disadvantageous for antibody interactions.…”

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

“…The World Health Organization has declared the outbreak of COVID-19 a global health emergency. To overcome this situation, a great amount of effort has been made in various research fields, including computational studies using the FMO method. − For example, Hatada et al reported an interaction analysis between the SARS-CoV-2 main protease and its inhibitor N3 using the FMO method. Akisawa et al also performed FMO calculations for SARS-CoV-2 spike proteins (S-protein) complexed with angiotensin-converting enzyme 2 (ACE2) and B38 antibody, in which the fourth-order Møller–Plesset perturbation (MP4) theory was employed.…”

Machine‐learning assisted scheduling optimization and its application in quantum chemical calculations

“…The QM models can be used only for reasonably modest system sizes (i.e., tens of atoms), while the fragment‐based approaches 15–31 or linear scaling strategies, 32–47 which a good load‐balancing scheme can benefit, are used to increase the reach of QM methods largely. For instance, there are many outstanding studies on analyzing the interactions, recognition of SARS‐CoV‐2 spike protein in QM level using fragment molecular orbital (FMO) approach 48–52 and molecular fractionation with conjugate caps (MFCC) approaches 53,54 …”

“…The QM models can be used only for reasonably modest system sizes (i.e., tens of atoms), while the fragment-based approaches [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] or linear scaling strategies, [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] which a good loadbalancing scheme can benefit, are used to increase the reach of QM methods largely. For instance, there are many outstanding studies on analyzing the interactions, recognition of SARS-CoV-2 spike protein in QM level using fragment molecular orbital (FMO) approach [48][49][50][51][52] and molecular fractionation with conjugate caps (MFCC) approaches. 53,54 As we have already entered the exascale super-computing era, 55 high-performance computing (HPC) is becoming progressively more important in bio-pharmaceutical systems, and achieving an even load balance is a key issue in practical computations.…”