Structures of MERS-CoV Macro Domain in Aqueous Solution with Dynamics:
Coupling Replica Exchange Molecular Dynamics and Deep Learning at the
Nano Level
Abstract
A novel virus, severe acute respiratory syndrome Coronavirus 2
(SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide
appeared in 2019. Currently, we do not have a medicament that treats the
disease. One of the rea-sons for the absence of treatment is related to
the scarcity of detailed scientific knowledge of the members of the
Coro-naviridae family, including the Middle East Respiratory Syndrome
Coronavirus (MERS-CoV). Structural studies of the MERS-CoV proteins in
the current literature are extremely limited. We present here detailed
characterization of the struc-tural properties of MERS-CoV macro domain
in aqueous solution at the atomic level with dynamics. For this study,
we conducted extensive replica exchange molecular dynamics simulations
linked to a generative neural networks and we use the resulting
trajectories for structural analysis. We perform structural clustering
based on the radius of gyration and end-to-end distance of MERS-CoV
macro domain in aqueous solution with dynamics at the atomic level. We
also report and analyze the residue-level intrinsic disorder features,
flexibility and secondary structure. Furthermore, we study the
pro-pensities of this macro domain for protein-protein interactions and
for the RNA and DNA binding. Results are in agree-ment with available
nuclear magnetic resonance spectroscopy findings and present more
detailed insights into the struc-tural properties of MERS CoV macro
domain. Overall, this work further shows that neural networks can be
used as an exploratory tool for the studies of CoV family molecular
conformational space at the nano level.