Molecular dynamics in multidimensional space explains how mutations affect the association path of neomycin to a riboswitch.

ABSTRACT: Riboswitches are messenger RNA (mRNA) fragments binding specific small molecules to regulate gene expression. A synthetic N1 riboswitch, inserted into yeast mRNA controls the translation of a reporter gene in response to neomycin. However, its regulatory activity is sensitive to single-point RNA mutations, even those distant from the neomycin binding site. While the association paths of neomycin to N1 and its variants remain unknown, recent fluorescence kinetic experiments indicate a two-step process driven by conformational selection. This raises the question of which step is affected by mutations. To address this, we performed all-atom two-dimensional replica-exchange molecular dynamics simulations for N1 and U14C, U14C[Formula: see text], U15A, and A17G mutants, ensuring extensive confo

SUBMITTER: Chyzy P 

PROVIDER: S-EPMC11009640 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature