Molecular dynamics simulations of LysRS: an asymmetric state

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.