Molecular Dynamics Studies of Histo-Blood Group Antigen Blocking Human Immunoglobulin A Antibody and Escape Mechanism in Noroviruses Upon Mutation

Abstract Norovirus is the causing agent of acute gastroenteritis disease globally. Efforts in developing therapeutics against virus infection mostly fail due to emergence of drug resistance that is a consequence of presence of high mutation rates in virus genome during virus' life cycle. In this study, we computationally analyzed the affinity of a drug target, wild type VP1 envelope protein and its three variants to a therapeutic antibody FAB5I2. We have found that mutations break important hydrogen bonds and cause high fluctuations in residues that form VP1–FAB5I2 complex interface. In addition to changes in dynamics, we also revealed that the affinity of FAB5I2 to VP1 protein drops significantly upon mutations in terms of relative binding free energy.