Molecular simulations and virtual screening to investigate the structure and binding sites of the Influenza A virus Nuclear Export Protein

Patel, H. and Kukol, A 2022. Molecular simulations and virtual screening to investigate the structure and binding sites of the Influenza A virus Nuclear Export Protein. Women in Bioinformatics and Data Science. Online 20 - 22 Sep 2022

TitleMolecular simulations and virtual screening to investigate the structure and binding sites of the Influenza A virus Nuclear Export Protein
AuthorsPatel, H. and Kukol, A
TypeConference paper
Abstract

Infection with the influenza A virus can lead to significant respiratory illness and has caused serious pandemics in previous years. The nuclear export protein (NEP) is a conserved, multifunctional internal influenza A protein which plays major roles in the virus life cycle. One such role is binding to the matrix protein (M1) to export genetic material from the nucleus to enable the translation of mRNA into viral proteins. Unlike many other influenza A proteins, limited information on the NEP structure is known and the NEP is currently not targeted by antiviral inhibitors. Therefore, improved understanding of the NEP structure and its interactions could aid the design and development of novel antivirals; or the re-purposing of current drugs that could target the influenza A virus. In this presentation, findings based on the analysis of partially restrained conventional Molecular Dynamics (MD) simulations to model the structure of the NEP, as well as binding site predictions will be presented. Subsequent results from virtual screening studies against a selected binding site using two compound libraries revealing molecules which may bind with high affinity to evolutionary conserved regions of the NEP will be discussed. Furthermore, current work which focuses on enhanced conformational space sampling of the NEP in complex with the influenza A M1 protein by performing accelerated MD simulations will also be presented.

KeywordsInfluenza A
Nuclear export protein
Molecular Dynamics Simulation
Drug Discovery
Year2022
ConferenceWomen in Bioinformatics and Data Science
Publication dates
Published2022

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