The Utility of Docking Programs for the Characterization of Peptide Protein Interactions

Abstract

Characterized by headache, fever, dyspnea, and even acute respiration distress syndrome and multiple organ failure, COVID-19 is a disease caused by SARS-CoV-2. This virus enters the host cell via its Spike Glycoprotein, interacting with host cell transmembrane protein ACE2 (angiotensin II converting enzyme). Therefore, to develop drugs against this disease, Spike Glycoprotein of SARS-CoV-2 and its specific interactions with ACE2 has a great importance. Due to their unique specialties such as being flexible, biocompatible, and target-specific, peptides are perfect candidate for rational drug design. Therefore, peptide-based drug design against COVID-19 by targeting to block Spike-ACE2 interaction is thought to be one of the best strategies on preventing the entry of the virus. Here we studied the efficacy of various molecular docking programs (i. e., Autodock Vina, HADDOCK, HPEPDOCK etc.) in terms of their ability to identify the binding site, binding conformation, and binding affinity. To this end, we conducted two benchmarking studies to dock known small molecules and peptides onto proteins. In the first one, we chose neuraminidase protein as the receptor protein and commercial drugs such as Oseltamivir, Laninamivir, Zanamivir and Peramivir as ligands. These drugs are used against H1N1 influenza virus, and their binding characteristics are well studied. In the second one, we use the same set of programs to dock peptides onto Spike Glycoprotein. These peptides have been obtained from ACE2 protein, which takes place in the SpikeACE2 interaction site. Here, we discuss the results of the benchmarking studies and the efficacy of molecular docking programs for further design of peptide-based drugs against COVID-19.