In this article, we used a hybrid simulation method to sample the conformational space to characterize the structural dynamics and global motions of WT SARS-CoV-2 Mpro and 48 mutants, including several mutations that appear in P.1, B.1.1.7, B.1.351, B.1.525 and B.1.429+B.1.427 variants. Integrated Hybrid methods combining NMA and MD have been useful to study the correlation between the complex structural dynamics of macromolecules and their functioning mechanisms. Here, we applied this hybrid approach to elucidate the effects of mutation in the structural dynamics of SARS-CoV-2 Mpro, considering their flexibility, solvent accessible surface area analyses, global movements, and catalytic dyad distance. Furthermore, some mutants showed significant changes in their structural dynamics and conformation, which could lead to distinct functional properties.
The main protease of SARS-CoV-2 (called Mpro or 3CLpro) is essential for
processing polyproteins encoded by viral RNA. Macromolecules adopt
several favored conformations in solution depending on their structure
and shape, determining their dynamics and function. Integrated methods
combining the lowest-frequency movements obtained by Normal Mode
Analysis (NMA), and the faster movements from Molecular Dynamics (MD),
and data from biophysical techniques, are necessary to establish the
correlation between complex structural dynamics of macromolecules and
their function. In this article, we used a hybrid simulation method to
sample the conformational space to characterize the structural dynamics
and global motions of WT SARS-CoV-2 Mpro and 48 mutants, including
several mutations that appear in P.1, B.1.1.7, B.1.351, B.1.525 and
B.1.429+B.1.427 variants. Integrated Hybrid methods combining NMA and MD
have been useful to study the correlation between the complex structural
dynamics of macromolecules and their functioning mechanisms. Here, we
applied this hybrid approach to elucidate the effects of mutation in the
structural dynamics of SARS-CoV-2 Mpro, considering their flexibility,
solvent accessible surface area analyses, global movements, and
catalytic dyad distance. Furthermore, some mutants showed significant
changes in their structural dynamics and conformation, which could lead
to distinct functional properties.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.