Establishing comprehensive quaternary structural proteomes from genome sequence

Abstract A critical body of knowledge has developed through advances in protein microscopy, protein-fold modeling, structural biology software, availability of sequenced bacterial genomes, large-scale mutation databases, and genome-scale models. Based on these recent advances, we develop a computational platform that; i) computes the oligomeric structural proteome encoded by an organism’s genome; ii) maps multi-strain alleleomic variation, resulting in the structural proteome for a species; and iii) calculates the 3D orientation of proteins across subcellular compartments with angstrom-level precision. Using the platform, we; iv) compute the full quaternary E. coli K-12 MG1655 structural proteome; v) deploy structure-guided analyses to identify consequential mutations; and, in combination with a genome-scale model that computes proteome allocation, vi) obtain a draft 3D visualization of the proteome in a functioning cell. Thus, in conjunction with relevant datasets and computational models, we can now resolve genome-scale structural proteomes to obtain an angstrom-level understanding of whole-cell functions.