title: Structural effects of modified ribonucleotides and magnesium in transfer RNAs.
abstract: 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 tRNAPheand tRNAinit, Escherichia coli tRNAinitand HIV tRNALys. 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 Mg2+. Results showed a stabilizing effect associated with the presence of the modifications and Mg2+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 tRNAinitand limitations were observed in the conformation of E. coli tRNAinit, the presence of the modified nucleotides and of Mg2+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.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, SE-141 83 Huddinge, Sweden.
authors.forename: You
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 Penn Street, Baltimore, MD 21201, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, SE-141 83 Huddinge, Sweden. Electronic address: lennart.nilsson@ki.se.
authors.forename: Lennart
authors.initials: L
authors.lastname: Nilsson
mesh_terms: D004926:Escherichia coli / Q000737:chemistry; D006678:HIV / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D012343:RNA, Transfer / Q000737:chemistry*; D012265:Ribonucleotides / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry
chemical_list: D012265:Ribonucleotides; D012343:RNA, Transfer; D008274:Magnesium
keywords: Magnesium; Modified nucleotide; Molecular dynamics; Nucleic acids; Structure; Transfer RNA