Structures of MERS-CoV macro domain in aqueous solution with dynamics: Impacts of parallel tempering simulation techniques and\n CHARMM36m\n and\n AMBER99SB\n force field parameters
Citation
Akbayrak İ. Y., Cağlayan Ş. İ., Durdağı, S., Coşkuner Weber, O., Hasekioğlu, O., Haklıdır, M., Dervişoğlu, H. (2021). Structures of MERS-CoV macro domain in aqueous solution with dynamics: Impacts of parallel tempering simulation techniques and\n CHARMM36m\n and\n AMBER99SB\n force field parameters. 89(10):1289–1299.Abstract
A novel virus, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), causing
coronavirus disease 2019 (COVID-19) worldwide appeared in 2019. Detailed scientific
knowledge of the members of the Coronaviridae family, including the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is currently lacking. Structural studies of the
MERS-CoV proteins in the current literature are extremely limited. We present here
detailed characterization of the structural properties of MERS-CoV macro domain in aqueous solution. Additionally, we studied the impacts of chosen force field parameters and parallel tempering simulation techniques on the predicted structural properties of MERS-CoV
macro domain in aqueous solution. For this purpose, we conducted extensive
Hamiltonian-replica exchange molecular dynamics simulations and Temperature-replica
exchange molecular dynamics simulations using the CHARMM36m and AMBER99SB
parameters for the macro domain. This study shows that the predicted secondary structure
properties including their propensities depend on the chosen simulation technique and
force field parameter. We perform structural clustering based on the radius of gyration and
end-to-end distance of MERS-CoV macro domain in aqueous solution. We also report and
analyze the residue-level intrinsic disorder features, flexibility and secondary structure. Furthermore, we study the propensities of this macro domain for protein-protein interactions
and for the RNA and DNA binding. Overall, results are in agreement with available nuclear
magnetic resonance spectroscopy findings and present more detailed insights into the
structural properties of MERS CoV macro domain in aqueous solution. All in all, we present
the structural properties of the aqueous MERS-CoV macro domain using different parallel
tempering simulation techniques, force field parameters and bioinformatics tools.
