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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 carbonyl with a Bürgi-Dunitz angle of 76-115°. Monomers with free energy minima that fall outside this conformational space do not react efficiently. This insight should accelerate the in vivo and in vitro ribosomal synthesis of sequence-defined, non-peptide heterooligomers.

SUBMITTER: Watson ZL

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

REPOSITORIES: biostudies-literature

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

Watson Zoe L ZL Knudson Isaac J IJ Ward Fred R FR Miller Scott J SJ Cate Jamie H D JHD Schepartz Alanna A Abramyan Ara M AM

Nature chemistry 20230612 7

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 ribo ...[more]

PMID: 37308707

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Project description:The aim of this study was to evaluate the genetic component of the locomotor jumping ability, via a wearable accelerometer sensor, and to estimate the genetic correlation with performance in competition, to introduce such criteria in selection schema. A sample of 1,056 young 3-year-old horses were equipped with a 3-dimensional accelerometer during a free jumping test, in regular breeding shows from 2015 to 2017. Seven variables were extracted from the dorso-ventral acceleration curve for the last three jumps over a double bar obstacle of 1.15 m for the front pole and 1.20 m for the back pole with a 1.20 m spread. Variables were the peaks of forelimbs, hindlimbs, and landing acceleration, the duration between peaks at take-off, the peak of forelimb acceleration and start of jump, jump duration and duration between the beginning of the impact of forelimbs and the peak at landing. During breeding shows, judges scored balance, strength, style, and reactivity for free jumping and jumping tests under saddle. Jumping competition results were recorded by logarithm of the sum of points earned in each competition. All horses in official competitions were included, i.e., 160,257 horses born in 1997 with a total of 649,491 annual performances. An animal mixed model with complete pedigree over four generations (353,236 horses) were used with fixed effects of jumping test location and date, morning/afternoon, gender, month of birth, rank of jump for accelerometric data, effect of year of competition, combined with age and gender for competition results. As a result, jump duration was the most heritable and repeatable for jump variables: h 2 = 0.16 (0.06), r = 0.52 (0.02), while accelerations were moderately heritable (h 2 = 0.05-0.09, r = 0.39-0.51). Judgement scores were heritable: 0.21 (0.07)-0.33 (0.09) and were highly correlated. Scores during free jumping were genetically correlated to jump duration: 0.71 (0.15)-0.88 (0.16). Both jump duration and judgement scores were genetically correlated to competition performance: 0.59 (0.13) for jump duration, from 0.60 (0.11) to 0.77 (0.12) for scores. Jump duration and judgement scores can be used as early selection criteria. The advantage of the accelerometric measurement is its objectivity and the ease of recording.

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

Publications

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

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