TCB Publications - Abstract

A. Singharoy, C. Maffeo, K. Delgardo, D. J. K. Swainsbury, M. Sener, U. Kleinekathöfer, B. Isralewitz, I. Teo, D. Chandler, J. Stone, J. Phillips, T. Pogorelov, M. I. Mallus, C. Chipot, Z. Luthey-Schulten, P. Tieleman, C. N. Hunter, Emad Tajkhorshid, A. Aksimentiev, and K. Schulten. Atoms to phenotypes: Molecular design principles of cellular energy metabolism. Cell, 179:1098-1111, 2019.

SING2019A Bioenergetic membranes are the key cellular structures responsible for coupled energy-conversion processes, which supply ATP and important metabolites to the cell. Here, we report the first 100-million atom-scale model of an entire photosynthetic organelle, a chromatophore membrane vesicle from a purple bacterium, which reveals the rate-determining steps of membrane-mediated energy conversion. Molecular dynamics simulations of this bioenergetic organelle elucidate how the network of bioenergetic proteins influences membrane curvature and demonstrates the impact of thermal disorder on photosynthetic excitation transfer. Brownian dynamics simulations of the quinone and cytochrome $c_2$ charge carriers within the chromatophore interior probe the mechanisms of nanoscale 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. Put together, the hybrid structure determination and systems-level modeling of the chromatophore, in conjunction with optical spectroscopy, illuminate the chemical and organizational design principles of biological membranes that foster energy storage and transduction in living cells. Parallels are drawn with the more universal mitochondrial bioenergetic machinery, from whence molecular-scale insights on the mechanism of cellular aging are inferred. This endeavor made feasible through the advent of petascale supercomputers, paves the way to first-principles modeling of whole living cells.

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