Abstract
While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes.
Highlights
Crick first predicted the existence of Transfer RNA molecules that mediate the translation of messenger RNA codons into corresponding amino acids even before they were discovered [1].The basis for his hypothesis is that while the 20 standard amino acids have great variability in sidechain types including hydrophobic, hydrophilic, charged, and aromatic moieties, nucleic acid bases form hydrogen bonds that are very good at identifying each other but not at distinguishing between different hydrophobic and hydrophilic species
Empirical force field molecular dynamics (MD) simulations are a class of simulations where biomolecular interactions are based on force field parameters [18]; these were originally intended to study the dynamics of proteins in the native basin
Since the first predictions of both Transfer RNA (tRNA) and aminoacyl-tRNA synthetases, these macromolecules have been subjected to decades of extensive experimental studies largely due to their fundamental roles in protein synthesis
Summary
Crick first predicted the existence of Transfer RNA (tRNA) molecules that mediate the translation of messenger RNA (mRNA) codons into corresponding amino acids even before they were discovered [1] The basis for his hypothesis is that while the 20 standard amino acids have great variability in sidechain types including hydrophobic, hydrophilic, charged, and aromatic moieties, nucleic acid bases form hydrogen bonds that are very good at identifying each other but not at distinguishing between different hydrophobic and hydrophilic species. The two N-terminal domains (red), catalytic domain (green), linker (cyan), and anticodon binding domain (orange) of ThrRS are shown in a ribbon diagram For both structures, the tRNAs are shown in a stick diagram (blue) with a trace of its backbone (yellow). Class II AARSs catalyze nucleophilic attack on the adenylate using the A76 3ʹ-hydroxyl; class I enzymes use the 2ʹ-OH for initial attack before transesterification to the 3ʹ-position
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