# Large-scale simulations of ribosomal decoding

> **NIH NIH R01** · TRIAD NATIONAL SECURITY, LLC · 2024 · $330,388

## Abstract

Multi-drug resistant bacteria present an increasing problem in US hospitals. To design new antibiotics that
are effective against these bacteria, it is important to understand drug-target interactions and the targets
themselves. We will study a major antibiotic target: the ribosome. Many ribosome antibiotics interfere with
the process of decoding by the ribosome ("tRNA selection"). The rate-limiting step of decoding is
accommodation, where the tRNA moves from a partially bound state (A/T state) to its fully bound position
(A/A state) inside the ribosome. Structural biology techniques have determined the structure of the
ribosome before and after accommodation. Kinetic experiments have determined accommodation rates. It
is difficult, however, to study the process of accommodation in atomic detail experimentally and the
detailed effects of antibiotics. While molecular dynamics simulations have been used to characterize
spontaneous transitions in smaller protein complexes, the large size and complexity of the ribosome have
made similar studies of the ribosome computationally prohibitive. In our preliminary data, we have
combined the high performance computing resources at Los Alamos National Laboratory with all-atom
reduced-model potentials to study accommodation of tRNA into the ribosome. Here, we will use large-
scale molecular simulation to study key features of accommodation and the effects of antibiotics. We will
closely integrate molecular dynamics with single molecule studies to form a more coherent picture of
ribosome decoding.

## Key facts

- **NIH application ID:** 10756987
- **Project number:** 5R01GM072686-19
- **Recipient organization:** TRIAD NATIONAL SECURITY, LLC
- **Principal Investigator:** Karissa Y Sanbonmatsu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $330,388
- **Award type:** 5
- **Project period:** 2005-07-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756987

## Citation

> US National Institutes of Health, RePORTER application 10756987, Large-scale simulations of ribosomal decoding (5R01GM072686-19). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10756987. Licensed CC0.

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