Hybrid QM/MM simulations in NAMD and VMD

Setting up the Genetic Code — Investigating the GluRS:tRNA:Glu-AMP complex, the aminoacylation reaction mechanism was studied to distinguish between four possible mechanisms. Uniting Network Analysis results for the full complex with the first combination of the string method, parallel eABF, and QM/MM simulations, provides an unique view for essential steps in establishing the genetic code.

Galactose switch in S. cerevisiae

Galactose switch induction — Lattice microbes simulation of the induction of the galactose switch in a S. cerevisiae cell. New galactose transporters (G2) represented by cyan spheres appear on the plasma membrane.

Expression of a galactose transporter — The birth of a galactose transporter is followed in a Lattice Microbes simulation.

Ribosome biogenesis in E. coli

Toward a Whole-Cell Model of Ribosome Biogenesis: Kinetic Modeling of SSU Assembly. T.M. Earnest, J. Lai, K. Chen, M.J. Hallock, J.R. Williamson, Z. Luthey-Schulten, Biophysical Journal, 2015, Sep 15, 109(5):1117-1135. doi:10.1016/j.bpj.2015.07.030

Ribosome biogenesis in replicating cells: Integration of experiment and theory T.M. Earnest, J.A. Cole, J.R. Peterson, M.J. Hallock, T. E. Kuhlman, Z. Luthey-Schulten, Biopolymers, 2016, Jul 22, 105(10):735-751, doi:10.1002/bip.22892

Ribosome biogenesis cartoon — A cartoon description of the ribosome biogenesis model in an E. coli cell.

Ribosome biogenesis — A dividing E. coli cell simulated with Lattice Microbes. Small subunit intermediates are shown in shades of green–cyan–blue. Translation initiation and termination events are shown as yellow and pink bubbles respectively. The purple region represents the nucleoid, containing the bulk of the DNA of the cell.

Heterogeneity in E. coli Colonies

Parametric Studies of Metabolic Cooperativity in Escherichia coli Colonies: Strain and Geometric Confinement Effects. J.R. Peterson, J.A. Cole, Z. Luthey-Schulten, PLoS ONE, 2017, Aug 18, 12(8):e0182570. doi: 10.1371/journal.pone.0182570

Macroscopic E. coli Colony — Visualization of an E. coli colony growing on an flat agar surface. Spatial gradients drive the colony into distinct crossfeeding metabolic phenotypes that anaerobically ferment glucose to acetate (red) or aerobically consume acetate (green).

Macroscopic E. coli Colony Growing Next to an Edge — Visualization of an E. coli colony growing near a 90 degree edge in an agar surface. Spatial gradients drive the colony into distinct crossfeeding metabolic phenotypes that anaerobically ferment glucose to acetate (red) or aerobically consume acetate (green).

The lac Genetic Switch in E. coli

Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study. E. Roberts, A. Magis, J.O. Ortiz, W. Baumeister, and Z. Luthey-Schulten. PLoS. Comput. Biol., 7(3):e1002010, 2011

E.coli Colony — A model of the lac genetic switch in a colony of fast-growing E. coli cells. Here we see LacY in yellow, and bursts of mRNA in pink. As we watch these cells respond to environmental Lactose we can see the stochastic nature of protein production and gene regulation in progress as two cells switch from an uninduced basal LacY state to an induced high-LacY state.

Repressor Rebinding — Here we see explore the role of crowding in the microscopic dynamics of a repressor, shown in white, unbinding and rebinding the lac operator, shown in pink. Obstacles appearing here are ribosomes in orange, large protein complexes in light green, and small complexes and individual proteins in dark green. The chromosome is shown here in red.

Slow Growth Cell w/ Ribosomes — A model of the lac genetic switch in a single slow-growing E. coli cell. The ribosomes are clearly visible in grey, particularly toward the ends, and their locations were taken from tomogram data. We can see LacY proteins in yellow, and bursts of mRNA in red in the viscinity of the Lac operator, shown green when bound to a repressor and white when unbound and capable of being transcribed.

Slow Growth Cell w/out Ribosomes — The same lac genetic switch model in a slow-growing cell as above, but with the ribosomes removed for clarity. The distinct condensed nucleoid region appearing here and above was formed using a biased random walk algorithm.

Repressor Binding in Slow Growth Cell — Here we highlight the dynamics of the repressors, seen here in the cytosol in light blue when bound to a single lactose, and darker blue when doubly bound.