Theoretical and Computational Chemistry

Computational Prediction of Mutational Effects on the SARS-CoV-2 Binding by Relative Free Energy Calculations


The ability of coronaviruses to infect humans is invariably associated with their binding strengths to human receptor proteins. Both SARS-CoV-2, initially named 2019-nCoV, and SARS-CoV were reported to utilize angiotensin-converting enzyme 2 (ACE2) as an entry receptor in human cells. To better understand the interplay between SARS-CoV-2 and ACE2, we performed computational alanine scanning mutagenesis on the “hotspot” residues at protein-protein interfaces using relative free energy calculations. Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV. In addition, our free energy calculations provide insight into the infectious ability of viruses on a physical basis, and also provide useful information for the design of antiviral drugs.

Version notes

This is an updated version (v03)


Thumbnail image of SARS-CoV-2-RBD-ACE2-FEP_v03.pdf

Supplementary material

Thumbnail image of SARS-CoV-2-RBD-ACE2-FEP_v03_SI.pdf