Effects of G198R Mutation in the Ebola VP40 Matrix Protein: A Molecular Dynamics Study

Abstract

Ebola and Marburg viruses are extremely dangerous zoonotic viruses that belong to the Filovirus family. In order to develop new vaccines and drugs to treat these viruses, it is crucial to understand the molecular level details of the virus life cycle. Out of seven different Ebola proteins, VP40 is the major matrix protein which is responsible for virion assembly, viral transcription and budding. The VP40 protein interacts with the host-cell membrane where it forms various higher order oligomers. The interaction of a VP40 dimer with the host cell membrane is one of the important steps in the viral life cycle. In this work, we study effects of G198R mutation on the VP40 dimer and membrane association. We observed that G198R mutation changes the basic loop conformation, thereby increasing the lipid interactions by facilitating a larger number of hydrogen bonds with lipid head groups. This atomic-level detailed information of how a single amino-acid substitution affects membrane binding might be useful for developing drug molecules that target the Ebola virus.