A Physics-based Approach of Coarse-graining the cytoplasm of E. coli

We have investigated protein stability in an environment of E. 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 developed a self-assembled clustering algorithm (CGCYTO). CGCYTO uses a tunable resolution parameter ($\lambda $, ranging from 0 to 1) to justify the resolution of a cytoplasm, depending on the size of a test protein for the computation of covolumes and the volume of a macromolecule in the cytoplasm. We compared the results from a polydisperse cytoplasm model (PD model) from CGCTYO with two other coarse-grained hard-sphere cytoplasm models: (1) F70 model, macromolecules in the cytoplasm were modeled by homogeneous hard spheres with a radius of 55{\AA} and (2) HS model, each macromolecule in the cytoplasm is modeled by hard spheres of various sizes. It was found that the folding temperature Tf of a test protein (apoazurin) is $\sim $5 degrees higher in a PD model than that in a F70 model. In addition, there is a deviation of 1.7 degrees on Tf when an apoazurin is randomly placed at different voids formed by particle fluctuations in a PD model, 0.7 degrees higher than that in a HS model.