Making Soup: Preparing and Validating Models of the Bacterial Cytoplasm for Molecular Simulation.

ABSTRACT

Biomolecular crowding affects the biophysical and biochemical behavior of macromolecules compared with the dilute environment in experiments on isolated proteins. Computational modeling and simulation are useful tools to study how crowding affects the structural dynamics and biological properties of macromolecules. With increases in computational power, modeling and simulation of large-scale all-atom explicit-solvent models of the prokaryote cytoplasm have now become possible. In this work, we built an atomistic model of the cytoplasm of Escherichia coli composed of 1.5 million atoms and submitted it to a total of 3 µs of molecular dynamics simulations. The model consisted of eight different proteins representing about 50% of the cytoplasmic proteins and one type of t-RNA molecule. Properties of biomolecules under crowding conditions were compared with those from simulations of the individual compounds under dilute conditions. The simulation model was found to be consistent with experimental data about the diffusion coefficient and stability of macromolecules under crowded conditions. In order to stimulate further work, we provide a Python script and a set of files to enable other researchers to build their own E. coli cytoplasm models to address questions related to crowding.