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. Proteins 2006. © 2005 Wiley‐Liss, Inc.