Atomistic simulations of the Escherichia coli ribosome provide selection criteria for translationally active substrates.

ABSTRACT: As genetic code expansion advances beyond L-α-amino acids to backbone modifications and new polymerization chemistries, delineating what substrates the ribosome can accommodate remains a challenge. The Escherichia coli ribosome tolerates non-L-α-amino acids in vitro, but few structural insights that explain how are available, and the boundary conditions for efficient bond formation are so far unknown. Here we determine a high-resolution cryogenic electron microscopy structure of the E. coli ribosome containing α-amino acid monomers and use metadynamics simulations to define energy surface minima and understand incorporation efficiencies. Reactive monomers across diverse structural classes favour a conformational space where the aminoacyl-tRNA nucleophile is <4 Å from the peptidyl-tRNA carb

SUBMITTER: Watson ZL 

PROVIDER: S-EPMC10322701 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature