A physics-based approach of coarse-graining the cytoplasm of Escherichia coli (CGCYTO)

We have investigated protein stability in an environment of Escherichia coli cytoplasm using coarse-grained computer simulations. To coarse-grain a small slide of E. coli's cytoplasm consisting of over 16 million atoms, we have developed a self-assembled clustering algorithm (CGCYTO). CGCYTO uses the shape parameter and asphericity as well as a parameter λ (ranging from 0 to 1) that measures the covolume of a test protein and a macromolecule against the covolume of a test protein and a sphere of equal volume as that of a macromolecule for the criteria of coarse-graining a cytoplasmic model. A cutoff λ_c = 0.8 was chosen based on the size of a test protein and computational resources and it determined the resolution of a coarse-grained cytoplasm. We compared the results from a polydisperse cytoplasmic model (PD model) produced by CGCYTO with two other coarse-grained hard-sphere cytoplasmic models: 1), F70 model, macromolecules in the cytoplasm were modeled by homogeneous hard spheres with a radius of 55 Å, the size of Ficoll70 and 2), HS model, each macromolecule in the cytoplasm was modeled by a hard sphere of equal volume. It was found that the folding temperature T_f of a test protein (apoazurin) in a PD model is ～5° greater than that in a F70 model. In addition, the deviation of T_f in a PD model is twice as much as that in a HS model when an apoazurin is randomly placed at different voids formed by particle fluctuations in PD models.