System-Level Simulation of a Bioenergetic Membrane

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 DESCRIPTION (provided by applicant): Bioenergetic membranes are a key cellular apparatus that carry out a series of interlinked energy conversion processes providing ATP and key metabolites for a cell. The individual processes and their underlying membrane proteins have been investigated intensively, but rarely have the processes been studied together, in particular not on the scale of a full organelle. The reasons are both lack of whole-membrane atomic resolution models and huge complexity. In case of a rather primitive, yet still representative bioenergetic membrane, namely the photosynthetic chromatophore of purple bacteria, the overall structure has been recently described in atomic detail, also huge with an atom count of 100 million; however, computational tools and computer power are available today to investigate the system as a whole. This proposal seeks funds to study the chromatophore in several steps: (1) A 100 million atom model of an entire chromatophore is built and simulated through molecular dynamics to describe its key physical properties, such as quinol/quinone diffusion in the lipid phase as well as overall redox-state-dependent electrostatics. (2) Structural insight gained from this detailed simulation guides subsequent multiscale simulations of the membrane-wide charge transport via protein (cytochrome c2) and lipid (quinone/quinol) diffusion and binding. (3) Dynamics of insertion of key bioenergetic proteins into the membrane through the ribosome-linked insertase YidC and the coupling between the stator and rotor domains in ATP synthase are described through molecular dynamics. The proposed study will provide the groundwork for future membrane-wide investigations of bioenergetic and other cellular organelles.