Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism

Abstract

We report the first 100-million atom-scale model of an entire cell organelle, a photosynthetic chromatophore vesicle from a purple bacterium, which reveals the cascade of energy-conversionsteps culminating into the generation of ATP from sunlight. Molecular dynamics simulations ofthis vesicle elucidate how the integral-membrane complexes influences local curvature as a ployto tune photoexcitation of pigments. Brownian dynamics of small-molecules within the chromatophore probe the mechanisms of directional charge transport under various pH and salinity conditions. Reproducing phenotypic properties from atomistic details, a rate-kinetic model evinces that low-light adaptations of the bacterium emerge as a spontaneous outcome of optimizing the balance between the chromatophore’s structural integrity and robust energy conversion. Parallels are drawn with the more universal mitochondrial bioenergetic machinery, from whence molecular-scale insights on the mechanism of cellular aging are inferred. Altogether, our integrative method and spectroscopic experiments pave the way to first-principles modeling of whole living cells.

Keywords: Cellular bioenergetics, Membrane sculpting, Charge transport, Photosynthesis, Respiration, Chromatophore, Macromolecular machines, Molecular networks, Integrative modeling, Computational chemistry, Molecular dynamics, Brownian dynamics, Systems Biology