Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism

Abhishek Singharoy, Christopher Maffeo, Karelia H. Delgado-Magnero, David J.K. Swainsbury, Melih Sener, Ulrich Kleinekathöfer, John W. Vant, Jonathan Nguyen, Andrew Hitchcock, Barry Isralewitz, Ivan Teo, Danielle E. Chandler, John E. Stone, James C. Phillips, Taras V. Pogorelov, M. Ilaria Mallus, Christophe Chipot, Zaida Luthey-Schulten, D. Peter Tieleman, C. Neil HunterEmad Tajkhorshid, Aleksei Aksimentiev, Klaus Schulten

Research output: Contribution to journalArticlepeer-review


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’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.
Original languageEnglish (US)
Pages (from-to)1098-1111.e23
Issue number5
StatePublished - Nov 14 2019


  • molecular dynamics simulation
  • MD
  • bioenergetics
  • chromatophore
  • photosynthesis
  • mitochondria
  • integrative model
  • biological membranes
  • charge transport
  • optical spectroscopy

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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