The Journal of Chemical Physics
Chaoyi Xu
Nidhi Katyal
Tanya Nesterova
Juan R. Perilla
Ebola virus (EBOV) is a human pathogen with the ability to cause hemorrhagic fever and bleeding diathesis in hosts. The life cycle of EBOV depends on its nucleocapsid. The nucleocapsid consists of a helical assembly of nucleoproteins (NPs) encapsidating single stranded viral RNA (ssRNA). Knowledge of the molecular determinants of Ebola nucleocapsid stability is essential for the development of therapeutics against EBOV. However, large degrees of freedom associated with the entire helical assembly pose a computational challenge, thereby limiting the previous simulation studies to the level of monomers. In the present work, we have performed all atom molecular dynamics (MD) simulations of the helical assembly of EBOV nucleoproteins in the absence and presence of ssRNA. We found that ssRNA is essential for maintaining structural integrity of the nucleocapsid. Other molecular determinants observed to stabilize the nucleocapsid include NP-RNA, NP-NP interactions and ion distributions. Additionally, the position of different components of the nucleocapsid in the helical assembly governs the structural and dynamical behavior of the nucleocapsid. NP monomers present on the longitudinal edges of the helical tube are more exposed, flexible and have weaker NP-NP interactions than those residing in the center. This work provides key structural features stabilizing the nucleocapsid that may serve as therapeutic targets.
in press
Computational Modeling