Bioorganic & medicinal chemistry 2016 Jun 1824(20) 4826-4834 pii 10.1016/j.bmc.2016.06.037
Modified nucleotides are ubiquitous and important to tRNA structure and function. To understand their effect on tRNA conformation, we performed a series of molecular dynamics simulations on yeast tRNA(Phe) and tRNAinit, Escherichia coli tRNAinit and HIV tRNA(Lys). Simulations were performed with the wild type modified nucleotides, using the recently developed CHARMM compatible force field parameter set for modified nucleotides (J. Comput. Chem.2016, 37, 896), or with the corresponding unmodified nucleotides, and in the presence or absence of Mg(2+). Results showed a stabilizing effect associated with the presence of the modifications and Mg(2+) for some important positions, such as modified guanosine in position 37 and dihydrouridines in 16/17 including both structural properties and base interactions. Some other modifications were also found to make subtle contributions to the structural properties of local domains. While we were not able to investigate the effect of adenosine 37 in tRNAinit and limitations were observed in the conformation of E. coli tRNAinit, the presence of the modified nucleotides and of Mg(2+) better maintained the structural features and base interactions of the tRNA systems than in their absence indicating the utility of incorporating the modified nucleotides in simulations of tRNA and other RNAs.