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Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism

76 Pages Posted: 5 Apr 2019 Sneak Peek Status: Published

See all articles by A. Singharoy

A. Singharoy

Arizona State University (ASU) - School of Molecular Sciences

C. Maffeo

University of Illinois at Urbana-Champaign - Department of Physics; University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

K.H. Delgado-Magnero

University of Calgary - Centre for Molecular Simulation; University of Calgary - Centre for Molecular Simulation

D. J. K. Swainsbury

University of Sheffield - Department of Molecular Biology and Biotechnology

M. Sener

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

U. Kleinekathöfer

Jacobs University Bremen - Department of Physics and Earth Sciences

B. Isralewitz

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

I. Teo

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

D. Chandler

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

J. W. Vant

Arizona State University (ASU) - School of Molecular Sciences

J. E. Stone

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

J. Phillips

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

T.V. Pogorelov

University of Illinois at Urbana-Champaign - Department of Chemistry

M. I. Mallus

Jacobs University Bremen - Department of Physics and Earth Sciences

C. Chipot

University of Illinois at Urbana-Champaign - Department of Physics; University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology; University of Lorraine - Laboratoire International Associé CNRS-UIUC

Z. Luthey-Schulten

University of Illinois at Urbana-Champaign - Department of Physics; University of Illinois at Urbana-Champaign - Department of Chemistry

P. Tieleman

University of Calgary - Centre for Molecular Simulation; University of Calgary - Department of Biological Sciences

C. N. Hunter

University of Sheffield - Department of Molecular Biology and Biotechnology

E. Tajkhorshid

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology; University of Illinois at Urbana-Champaign - Center for Biophysics and Quantitative Biology

A. Aksimentiev

University of Illinois at Urbana-Champaign - Department of Physics; University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology; University of Illinois at Urbana-Champaign - Center for Biophysics and Quantitative Biology

K. Schulten

University of Illinois at Urbana-Champaign - Department of Physics; University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

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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

Suggested Citation

Singharoy, A. and Maffeo, C. and Delgado-Magnero, K.H. and Swainsbury, D. J. K. and Sener, M. and Kleinekathöfer, U. and Isralewitz, B. and Teo, I. and Chandler, D. and Vant, J. W. and Stone, J. E. and Phillips, J. and Pogorelov, T.V. and Mallus, M. I. and Chipot, C. and Luthey-Schulten, Z. and Tieleman, P. and Hunter, C. N. and Tajkhorshid, E. and Aksimentiev, A. and Schulten, K., Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism (April 3, 2019). Available at SSRN: https://ssrn.com/abstract=3365009 or http://dx.doi.org/10.2139/ssrn.3365009
This is a paper under consideration at Cell Press and has not been peer-reviewed.

A. Singharoy (Contact Author)

Arizona State University (ASU) - School of Molecular Sciences ( email )

Tempe, AZ 85287
United States

C. Maffeo

University of Illinois at Urbana-Champaign - Department of Physics

601 E John St
Champaign, IL 61820
United States

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

K.H. Delgado-Magnero

University of Calgary - Centre for Molecular Simulation

University Drive
Calgary, T2N 1N4
Canada

University of Calgary - Centre for Molecular Simulation

University Drive
Calgary, T2N 1N4
Canada

D. J. K. Swainsbury

University of Sheffield - Department of Molecular Biology and Biotechnology

United Kingdom

M. Sener

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

U. Kleinekathöfer

Jacobs University Bremen - Department of Physics and Earth Sciences

Bremen
Germany

B. Isralewitz

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

I. Teo

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

D. Chandler

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

J. W. Vant

Arizona State University (ASU) - School of Molecular Sciences

Tempe, AZ 85287
United States

J. E. Stone

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

J. Phillips

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

T.V. Pogorelov

University of Illinois at Urbana-Champaign - Department of Chemistry

601 E John St
Champaign, IL 61820
United States

M. I. Mallus

Jacobs University Bremen - Department of Physics and Earth Sciences

Bremen
Germany

C. Chipot

University of Illinois at Urbana-Champaign - Department of Physics

601 E John St
Champaign, IL 61820
United States

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

University of Lorraine - Laboratoire International Associé CNRS-UIUC

Lorraine
France

Z. Luthey-Schulten

University of Illinois at Urbana-Champaign - Department of Physics

601 E John St
Champaign, IL 61820
United States

University of Illinois at Urbana-Champaign - Department of Chemistry

601 E John St
Champaign, IL 61820
United States

P. Tieleman

University of Calgary - Centre for Molecular Simulation

University Drive
Calgary, T2N 1N4
Canada

University of Calgary - Department of Biological Sciences

University Drive
Calgary, Alberta T2N 1N4
Canada

C. N. Hunter

University of Sheffield - Department of Molecular Biology and Biotechnology

United Kingdom

E. Tajkhorshid

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

University of Illinois at Urbana-Champaign - Center for Biophysics and Quantitative Biology

Urbana, IL 61801
United States

A. Aksimentiev

University of Illinois at Urbana-Champaign - Department of Physics

601 E John St
Champaign, IL 61820
United States

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

University of Illinois at Urbana-Champaign - Center for Biophysics and Quantitative Biology

Urbana, IL 61801
United States

K. Schulten

University of Illinois at Urbana-Champaign - Department of Physics

601 E John St
Champaign, IL 61820
United States

University of Illinois at Urbana-Champaign - Beckman Institute for Advanced Science and Technology

601 E John St
Champaign, IL 61820
United States

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