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Principal Investigator

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P25  Gerhard Hummer
Director

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Department of
Theoretical Biophysics
Max Planck Institute of Biophysics
Max-von-Laue-Str. 3
60438 Frankfurt am Main, Germany

Phone +49 (0)69 6303-2501
Fax +49 (0)69 6303-2502

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P25 Atomistic simulation and modeling of active membrane transport


Understanding the mechanisms of active membrane transport is a central theme of the CRC 807. Project P25 will use atomistic molecular dynamics (MD) simulations and modeling to study the function of key proteins involved in active transport, working closely with the experimental groups within the Center. MD simulations make it possible to monitor biomolecular systems with atomic resolution as they carry out their functions. Simulation and modeling thus complement and extend the structural, biochemical and biophysical studies carried out within the CRC.

We will concentrate on two systems: the modeling and simulation of proton-coupled rotary motion in ATP synthase, on the basis of the recent ATP synthase dimer structure from the Kühlbrandt lab (P01); and of ABC transporter function on the basis of the recent structure of TmrAB from the Tampé lab (P16). Key questions to be addressed by the MD simulations of ATP synthase concern (i) proton access and release in the Fo motor, (ii) the coupling of this transmembrane proton transfer to the rotatory motion of its c-ring, and (iii) the transmission of this motion to the F1 motor via the rotor shaft and its interface with the c-ring. In the ABC transporter study, we will investigate (i) substrate binding, (ii) its coupling to closure of the ATP binding sites, and (iii) the associated global conformational dynamics.

The results of the atomistic MD simulations will provide a basis for the development of detailed, quantitative, and experimentally testable models of the mechanochemical coupling in ATP synthase and ABC transporter function. We will also provide modeling and simulation support to other projects within the CRC.

 

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Publications

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Hummer G, Fricke F, Heilemann M (2016) Model-independent counting of molecules in single-molecule localization microscopy. Mol Biol Cell 27, 3637-44.

Covino C, Ballweg S, Stordeur C, Michaelis JB, Pesek K, Wernig F, Bahrami A, Ernst AM, Hummer G, Ernst R (2016) A eukaryotic sensor for membrane lipid saturation. Mol Cell 63, 49-59.

Mehdipour AR, Hummer G (2016) Cardiolipin puts the seal on ATP synthase. Proc Natl Acad Sci USA 113, 8568-70.

Hummer G, Wikström M (2016) Molecular simulation and modeling of complex I. Biochim Biophys Acta-Bioenergetics 1857, 915-21.

Sugawa M, Okazaki KI, Kobayashi M, Matsui T, Hummer G, Masaike T, Nishizaka T (2016) F1-ATPase conformational cycle from simultaneous single-molecule FRET and rotation measurements. Proc Natl Acad Sci USA 113, E2916-24.

Barends TRM, Foucar L, Ardevol A, Nass K, Aquila A, Botha S, Doak RB, Falahati K, Hartmann E, Hilpert M, Heinz M, Hoffmann MC, Köfinger J, Koglin JE, Kovacsova G, Liang M, Milathianaki D, Lemke H, Reinstein J, Roome CM, Shoeman RL, Williams GJ, Burghardt I, Hummer G, Boutet S, Schlichting I (2015) Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation. Science 350, 445-50. 


Blees A, Reichel K, Trowitzsch S, Fisette O, Bock C, Abele R, Hummer G, Schäfer L, Tampé R (2015) Assembly of the MHC I peptide-loading complex determined by a conserved ionic lock-switch. Sci Rep 5, 17341.

Okazaki K, Hummer G (2015) Elasticity, friction, and pathway of gamma-subunit rotation in FoF1-ATP synthase. Proc Natl Acad Sci USA 112, 10720-5.


Sharma V, Belevich G, Gamiz-Hernandez AP, Róg T, Vattulainen I, Verkhovskaya ML, Wikström M, Hummer G, Kaila VRI (2015) Redox-induced activation of the proton pump in the respiratory complex I. Proc Natl Acad Sci USA 112, 11571-6.

Wikström M, Sharma V, Kaila VRI, Hosler JP, Hummer G (2015) New perspectives on proton pumping in cellular respiration. Chem Rev 115, 2196-221. 


Hummer G (2014) Potassium ions line up. Do K+ ions move in single file through potassium channels? Science 346, 303.

Johnson ME, Hummer G (2014) Free-propagator reweighting integrator for single-particle dynamics in reaction-diffusion models of heterogeneous protein-protein interaction systems. Phys Rev X 4, 031037.

Rosta E, Yang W, Hummer G (2014) Calcium inhibition of ribonuclease H1 two-metal ion catalysis. J Am Chem Soc 136, 3137-44.

Kaila VRI, Wikström M, Hummer G (2014) Electrostatics, hydration, and proton transfer dynamics in the membrane domain of respiratory complex I. Proc Natl Acad Sci USA 111, 6988-93.

Kaila VRI, Schotte F, Cho HS, Hummer G, Anfinrud PA (2014) Reconciling contradictions in time-resolved x-ray structures of early intermediates in the photocycle of photoactive yellow protein. Nature Chemistry 6, 258-9. 

Cossio P, Hummer G (2013) Bayesian analysis of individual electron microscopy images: Towards structures of dynamic and heterogeneous biomolecular assemblies. J Struct Biol 184, 427-437.

Hummer G (2013) Nobel 2013 – Methods for computational chemistry. Computer experiments. Nature 504, 96-97.

Best RB, Hummer G, Eaton WA (2013) Native contacts determine protein folding mechanisms in atomistic simulations. Proc Natl Acad Sci USA 110, 17874-9.

Okazaki KI, Hummer G (2013) Phosphate release coupled to rotary motion of F1-ATPase. Proc Natl Acad Sci USA 110, 16468-73. 

Zhu FQ, Hummer G (2010) Pore opening and closing of a pentameric ligand-gated ion channel. Proc Natl Acad Sci USA 107, 19814-9. 

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Collaborations

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Kühlbrandt (P01), Prisner/Joseph (P07), Abele (P09), Wachtveitl/Bamann (P12),
Schwalbe (P13), Müller (P14),  Tampé (P16), Heilemann (P20), Ernst (P21), Hänelt (P22)