title: Molecular dynamics simulations of LysRS: an asymmetric state.
abstract: We report molecular dynamics simulations of the Escherichia coli Lysyl-tRNA synthetase LysU isoform carried out as a benchmark for mutant simulations in in silico protein engineering efforts. Unlike previous studies of aminoacyl-tRNA synthetases, LysU is modelled in its full dimeric form with explicit solvent. While developing a suitable simulation protocol, we observed an asymmetry that persists despite improvements to the model. This prediction has directly led to experiments that establish a functional asymmetry in nucleotide binding by LysU. The development of a simulation protocol and validation of the model are presented here. The observed asymmetry is described and the role of protein flexibility in developing the asymmetry is discussed.
authors.affiliation: Imperial College Genetic Therapies Centre, Department of Chemistry, Imperial College London.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Hughes
authors.forename: Julian A
authors.initials: JA
authors.lastname: Tanner
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.forename: Ian R
authors.initials: IR
authors.lastname: Gould
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D029968:Escherichia coli Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008250:Lysine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008962:Models, Theoretical; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D029968:Escherichia coli Proteins; D000255:Adenosine Triphosphate; D008250:Lysine-tRNA Ligase; D008239:Lysine