Solution Domain Dynamics of Monomeric SARS-CoV‑2 Main Protease Revealed by Optimized NMR Residual Dipolar Coupling Measurements.

ABSTRACT: The main protease (MPro) of SARS-CoV-2, released from a monomeric precursor, is essential for viral replication, and multiple antiviral compounds target the active site of the mature dimer. However, the solution structure and dynamics of the monomer remain poorly understood. Here, we utilize residual dipolar couplings (RDCs) to characterize conformational and dynamical differences between monomeric and dimeric MPro. While most protein NMR studies rely primarily on ¹H-¹⁵N RDCs, we demonstrate that at least four backbone RDCs can be measured at high accuracy from a single aligned sample. We compare frequency-based and intensity-based methods and introduce a mixed-time evolution scheme that improves resolution in 2D N-C' RDC measurements. These methods are applied to a 9

SUBMITTER: Smith MJ 

PROVIDER: S-EPMC12856667 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature