Challenges of Integrating Stochastic Dynamics and Cryo-Electron Tomograms in Whole-Cell Simulations.
J Phys Chem B
; 121(15): 3871-3881, 2017 04 20.
Article
em En
| MEDLINE
| ID: mdl-28291359
ABSTRACT
Cryo-electron tomography (cryo-ET) has rapidly emerged as a powerful tool to investigate the internal, three-dimensional spatial organization of the cell. In parallel, the GPU-based technology to perform spatially resolved stochastic simulations of whole cells has arisen, allowing the simulation of complex biochemical networks over cell cycle time scales using data taken from -omics, single molecule experiments, and in vitro kinetics. By using real cell geometry derived from cryo-ET data, we have the opportunity to imbue these highly detailed structural data-frozen in time-with realistic biochemical dynamics and investigate how cell structure affects the behavior of the embedded chemical reaction network. Here we present two examples to illustrate the challenges and techniques involved in integrating structural data into stochastic simulations. First, a tomographic reconstruction of Saccharomyces cerevisiae is used to construct the geometry of an entire cell through which a simple stochastic model of an inducible genetic switch is studied. Second, a tomogram of the nuclear periphery in a HeLa cell is converted directly to the simulation geometry through which we study the effects of cellular substructure on the stochastic dynamics of gene repression. These simple chemical models allow us to illustrate how to build whole-cell simulations using cryo-ET derived geometry and the challenges involved in such a process.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Microscopia Crioeletrônica
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Tomografia com Microscopia Eletrônica
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Simulação de Dinâmica Molecular
Limite:
Humans
Idioma:
En
Revista:
J Phys Chem B
Ano de publicação:
2017
Tipo de documento:
Article