MULTISCALE AND INTEGRATIVE MODELLING OF THE FLAVIVIRUS C PROTEIN AND ITS INTERACTIONS

Abstract

The DENV and ZIKV C protein is a small multifunctional ∼100 amino acid long protein that forms homodimers in solution. It packages the genomic single stranded RNA within the viral particle to form the nucleocapsid. The architecture of the flavivirus nucleocapsid and its components remains an active area of research as its inherent size and disorderedness precludes structure based techniques such as cryo-EM, X-ray crystallography and NMR. The C protein itself contains an ordered core region and intrinsically disordered tails that makes the study of these proteins challenging but are essential for its multi-functionality. In this thesis, multiscale simulations and bioinformatics techniques were used to probe the dynamics of the C protein and its interactions with the genomic RNA and lipid membranes. This thesis represents an intensive study of the flavivirus C protein and its interactions and contribute to the knowledge of this multifunctional protein