title: Efficient Multiscale Models of Polymer Assembly.
abstract: Protein polymerization and bundling play a central role in cell physiology. Predictive modeling of these processes remains an open challenge, especially when the proteins involved become large and their concentrations high. We present an effective kinetics model of filament formation, bundling, and depolymerization after GTP hydrolysis, which involves a relatively small number of species and reactions, and remains robust over a wide range of concentrations and timescales. We apply this general model to study assembly of FtsZ protein, a basic element in the division process of prokaryotic cells such as Escherichia coli, Bacillus subtilis, or Caulobacter crescentus. This analysis demonstrates that our model outperforms its counterparts in terms of both accuracy and computational efficiency. Because our model comprises only 17 ordinary differential equations, its computational cost is orders-of-magnitude smaller than the current alternatives consisting of up to 1000 ordinary differential equations. It also provides, to our knowledge, a new insight into the characteristics and functioning of FtsZ proteins at high concentrations. The simplicity and versatility of our model render it a powerful computational tool, which can be used either as a standalone descriptor of other biopolymers' assembly or as a component in more complete kinetic models.
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California-San Diego, La Jolla, California.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Ruiz-Martinez
authors.affiliation: Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bartol
authors.affiliation: Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California; The Division of Biological Studies Sciences, University of California-San Diego, La Jolla, California. Electronic address: terry@salk.edu.
authors.forename: Terrence J
authors.initials: TJ
authors.lastname: Sejnowski
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California-San Diego, La Jolla, California. Electronic address: dmt@ucsd.edu.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Tartakovsky
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria