@article{ccb505702eee4e819b864c3e0d0cf03a,
title = "Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism",
abstract = "We report a 100-million atom-scale model of an entire cell organelle, a photosynthetic chromatophore vesicle from a purple bacterium, that reveals the cascade of energy conversion steps culminating in the generation of ATP from sunlight. Molecular dynamics simulations of this vesicle elucidate how the integral membrane complexes influence local curvature to 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 kinetic model evinces that low-light adaptations of the bacterium emerge as a spontaneous outcome of optimizing the balance between the chromatophore{\textquoteright}s structural integrity and robust energy conversion. Parallels are drawn with the more universal mitochondrial bioenergetic machinery, from whence molecular-scale insights into the mechanism of cellular aging are inferred. Together, our integrative method and spectroscopic experiments pave the way to first-principles modeling of whole living cells.",
keywords = "molecular dynamics simulation, MD, bioenergetics, chromatophore, photosynthesis, mitochondria, integrative model, biological membranes, charge transport, optical spectroscopy",
author = "Abhishek Singharoy and Christopher Maffeo and Delgado-Magnero, {Karelia H.} and Swainsbury, {David J.K.} and Melih Sener and Ulrich Kleinekath{\"o}fer and Vant, {John W.} and Jonathan Nguyen and Andrew Hitchcock and Barry Isralewitz and Ivan Teo and Chandler, {Danielle E.} and Stone, {John E.} and Phillips, {James C.} and Pogorelov, {Taras V.} and Mallus, {M. Ilaria} and Christophe Chipot and Zaida Luthey-Schulten and Tieleman, {D. Peter} and Hunter, {C. Neil} and Emad Tajkhorshid and Aleksei Aksimentiev and Klaus Schulten",
note = "Funding Information: A.S. acknowledges start-up award funds from Arizona State University and grants from the Research Corporation for Science Advancement and the Gordon and Betty Moore Foundation; United States , Lightworks Foundation , and Flinn Foundation . E.T., A.A., C.M., A.S., C.C., B.I., I.T., D.C., J.E.S., and J.P. acknowledge NIH grants P41-GM104601 (PI: E.T.) and NIH R01-GM067887 (PI: E.T.). A.S., C.M., Z.L.-S., and A.A. acknowledge the Center for Physics of Living Cells ( NSF PHY-1430124 ). M.S. and Z.L.-S. also acknowledge NSF funding through MCB1616790 . T.V.P. acknowledges support from the Department of Chemistry , the School of Chemical Sciences , and the Office of the Vice Chancellor for Research at the University of Illinois at Urbana-Champaign . C.C. acknowledges support from the Contrat Plan {\'E}tat R{\'e}gion (CPER) IT2MP and the European Regional Development Fund (ERDF). Work in D.P.T.{\textquoteright}s group is supported by the Natural Sciences and Engineering Research Council (Canada) with further support from the Canada Research Chairs Program and Alberta Innovates Technology Futures . D.P.T. and K.H.D.M. acknowledge Compute Canada , funded by the Canada Foundation of Innovation and partners, for computational resources. U.K. acknowledges grant KL 1299/12-1 from the Deutsche Forschungsgemeinschaft (DFG). D.J.K.S., A.H., and C.N.H. acknowledge research grant BB/M000265/1 from the Biotechnology and Biological Sciences Research Council (UK). C.N.H. was also supported by advanced award 338895 from the European Research Council . The study was also funded by the Photosynthetic Antenna Research Center (PARC), an Energy Frontier Research Center supported by the Department of Energy , Office of Science , and Office of Basic Energy Sciences under award DE-SC0001035 (to C.N.H., K.S., and M.S.). This research used resources of the Oak Ridge Leadership Computing Facility, which is supported by the Office of Science , Department of Energy ( DE-AC05-00OR22725 ). Funding Information: A.S. acknowledges start-up award funds from Arizona State University and grants from the Research Corporation for Science Advancement and the Gordon and Betty Moore Foundation; United States, Lightworks Foundation, and Flinn Foundation. E.T. A.A. C.M. A.S. C.C. B.I. I.T. D.C. J.E.S. and J.P. acknowledge NIH grants P41-GM104601 (PI: E.T.) and NIH R01-GM067887 (PI: E.T.). A.S. C.M. Z.L.-S. and A.A. acknowledge the Center for Physics of Living Cells (NSF PHY-1430124). M.S. and Z.L.-S. also acknowledge NSF funding through MCB1616790. T.V.P. acknowledges support from the Department of Chemistry, the School of Chemical Sciences, and the Office of the Vice Chancellor for Research at the University of Illinois at Urbana-Champaign. C.C. acknowledges support from the Contrat Plan ?tat R?gion (CPER) IT2MP and the European Regional Development Fund (ERDF). Work in D.P.T.?s group is supported by the Natural Sciences and Engineering Research Council (Canada) with further support from the Canada Research Chairs Program and Alberta Innovates Technology Futures. D.P.T. and K.H.D.M. acknowledge Compute Canada, funded by the Canada Foundation of Innovation and partners, for computational resources. U.K. acknowledges grant KL 1299/12-1 from the Deutsche Forschungsgemeinschaft (DFG). D.J.K.S. A.H. and C.N.H. acknowledge research grant BB/M000265/1 from the Biotechnology and Biological Sciences Research Council (UK). C.N.H. was also supported by advanced award 338895 from the European Research Council. The study was also funded by the Photosynthetic Antenna Research Center (PARC), an Energy Frontier Research Center supported by the Department of Energy, Office of Science, and Office of Basic Energy Sciences under award DE-SC0001035 (to C.N.H. K.S. and M.S.). This research used resources of the Oak Ridge Leadership Computing Facility, which is supported by the Office of Science, Department of Energy (DE-AC05-00OR22725). Conceptualization, A.S. A.A. M.S. C.N.H. and K.S.; Methodology, A.S. M.S. C.M. A.A. U.K. C.C. D.P.T. Z.L.-S. and C.N.H.; Investigation, A.S. C.M. K.H.D.M. D.J.K.S. M.S. U.K. J.W.V. J.N. I.T. D.E.C. A.H. T.V.P. and M.I.M.; Writing ? Original Draft, A.S. A.A. K.H.D.M. M.S. C.C. Z.L.-S. E.T. and C.N.H.; Writing ? Review & Editing, J.W.V. J.N. A.S. A.A. C.C. K.H.D.M. M.S. U.K. D.P.T. E.T. D.J.K.S. and A.H.; Visualization, B.I. J.E.S. and A.S.; Funding Acquisition, A.S. E.T. Z.L.-S. A.A. and K.S.; Resources, A.S. J.C.P. J.E.S. A.A. Z.L.-S. and E.T.; Supervision, A.S. A.A. C.N.H. D.P.T. and K.S. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2019",
month = nov,
day = "14",
doi = "10.1016/j.cell.2019.10.021",
language = "English (US)",
volume = "179",
pages = "1098--1111.e23",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "5",
}