Accurate Evaluation on the Interactions of SARS-CoV-2 with Its Receptor ACE2 and Antibodies CR3022/CB6*

Abstract

The spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global health crisis. The binding affinity of SARS-CoV-2 (in particular the receptor binding domain, RBD) to its receptor angiotensin converting enzyme 2 (ACE2) and the antibodies is of great importance in understanding the infectivity of COVID-19 and evaluating the candidate therapeutic for COVID-19. We propose a new method based on molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) to accurately calculate the free energy of SARS-CoV-2 RBD binding to ACE2 and antibodies. The calculated binding free energy of SARS-CoV-2 RBD to ACE2 is –13.3 kcal/mol, and that of SARS-CoV RBD to ACE2 is –11.4 kcal/mol, which agree well with the experimental results of –11.3 kcal/mol and –10.1 kcal/mol, respectively. Moreover, we take two recently reported antibodies as examples, and calculate the free energy of antibodies binding to SARS-CoV-2 RBD, which is also consistent with the experimental findings. Further, within the framework of the modified MM/PBSA, we determine the key residues and the main driving forces for the SARS-CoV-2 RBD/CB6 interaction by the computational alanine scanning method. The present study offers a computationally efficient and numerically reliable method to evaluate the free energy of SARS-CoV-2 binding to other proteins, which may stimulate the development of the therapeutics against the COVID-19 disease in real applications.

Insights into the conformation changes of SARS-CoV-2 spike receptor-binding domain on graphene

“…After the RBD was stably absorbed, the last 30 ns of the simulated trajectory was used to calculate the binding free energy by the shell script gmx_mmpbsa [57] , [68] , with one frame at 1 ns interval. The results are shown in Fig.…”

“…The binding energy (BE) of each residue with graphene was also calculated using gmx_mmpbsa [57] , [68] , where the energy contributed by entropy was not included. The results are shown in Fig.…”

“…MM-PBSA is a method to calculate the binding free energy with the MD trajectory. It has been successfully applied into many researches in biomedical field [54] , [55] , [56] , [57] , [58] , [59] . The free energy of a molecule can be expressed as …”

Towards an optimal monoclonal antibody with higher binding affinity to the receptor-binding domain of SARS-CoV-2 spike proteins from different variants

“…As mentioned above, CR3022 has been suggested as a promising therapeutic option to neutralize SARS-CoV-2 (Barnes et al, 2020;Tian et al, 2020;Wu et al, 2020;Yuan et al, 2020), and is often explored in theoretical studies (Corrêa Giron et al, 2020;Ding et al, 2021;Nguyen et al, 2021;Shariatifar and Farasat, 2021). In a pioneer computational study at the very beginning of the pandemic, using constant-pH MC simulations, Giron, Laaksonen, and Barroso da Silva showed that CR3022 known to bind to SARS-CoV-1 RBD could also bind to SARS-CoV-2 RBD.…”

Loading of DOX into a tetrahedral DNA nanostructure: the corner does matter

“…64 In the binding energy calculation, the last 10 ns of each stabilized simulation trajectory was used with an interval of 100 ps, namely 100 frames for each run using the molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method. [65][66][67][68][69] The gmx_mmpbsa script (https://jerkwin.github.io/ gmxtool) together with the APBS 70,71 program were used to calculate the binding energy and the corresponding energy decomposition term, namely the electrostatic (ELE) energy, the van der Waals (VDW) energy, and the solvation energy including the polar part (PB) and the non-polar part (SA) in this work.…”