biostudies-literatureRosario PANational Institute of General Medical SciencesNIGMS NIH HHS1196-1200https://www.ebi.ac.uk/biostudies/studies/S-EPMC8284874biostudies-literatureUnknown22(7)Infection and replication of SARS CoV-2 (the virus that causes COVID-19) requires entry to the interior of host cells. In humans, a protein-protein interaction (PPI) between the SARS CoV-2 receptor-binding domain (RBD) and the extracellular peptidase domain of ACE2 on the surface of cells in the lower respiratory tract is an initial step in the entry pathway. Inhibition of the SARS CoV-2 RBD/ACE2 PPI is currently being evaluated as a target for therapeutic and/or prophylactic intervention. However, relatively little is known about the molecular underpinnings of this complex. Employing multiple computational platforms, we predicted "hot-spot" residues in a positive-control PPI (PMI/MDM2) and the CoV-2 RBD/ACE2 complex. Computational alanine scanning mutagenesis was performed to predict chanChembiochem : a European journal of chemical biologyComputational Hot-Spot Analysis of the SARS-CoV-2 Receptor Binding Domain/ACE2 Complex*.PMC8284874P20 GM103446P20GM103446McNaughton BRRosario PAfalseComputational Hot-Spot Analysis of the SARS-CoV-2 Receptor Binding Domain/ACE2 Complex*.Infection and replication of SARS CoV-2 (the virus that causes COVID-19) requires entry to the interior of host cells. In humans, a protein-protein interaction (PPI) between the SARS CoV-2 receptor-binding domain (RBD) and the extracellular peptidase domain of ACE2 on the surface of cells in the lower respiratory tract is an initial step in the entry pathway. Inhibition of the SARS CoV-2 RBD/ACE2 PPI is currently being evaluated as a target for therapeutic and/or prophylactic intervention. However, relatively little is known about the molecular underpinnings of this complex. Employing multiple computational platforms, we predicted "hot-spot" residues in a positive-control PPI (PMI/MDM2) and the CoV-2 RBD/ACE2 complex. Computational alanine scanning mutagenesis was performed to predict chan2021-01-01T00:00:00Z2021 Apr2026-05-31T06:03:04.044Z2025-02-19T01:55:17.218ZS-EPMC82848743317466910.1002/cbic.202000562