Bionanodevices are biomolecular complexes that self-assemble, recognize and control each other with the end of performing one overall function in living cells such as genetic expression, energy conversion, metabolism, signaling, and motion. Examples of bionanodevices are nucleosome and ribosome, ATPase, multienzyme complexes, actin and myosin, all systems the structures of which have recently been solved or are about to be solved. Combined computational-experimental studies have proven successful in explaining the structure--function relationship of proteins, but bionanodevices due to their size pose a great challenge to computational biologists that can be met only through advanced software and hardware.
Our group has built the tools needed for modeling bionanodevices, in particular, the molecular dynamics program NAMD that runs effectively on hundreds to thousands of processors and the molecular graphics program VMD.
The lecture will demonstrate how computational methods support and complement observation as well as integrate physical descriptions from the electronic to the multi-protein level. It will focus on two bionanodevices, the purple membrane (PM) of Halobacteria and the photosynthetic unit of purple bacteria (PSU).
The PM of Halobacterium salinarium converts sun light into a chemiosmotic potential. The membrane is a crystalline hexagonal array that contains a single protein, bacteriorhodopsin, and ten lipids per protein. Recent observations resolved the structure of most of the components and through modelling we have combined the data to build the entire purple membrane. This hexagonally periodic, lamellar model has been hydrated and refined through NpT/PME molecular dynamics simulations. The resulting structure connects extracellular bulk water with water molecules and key side groups in the interior of the membrane proteins, permitting a seamless overall description of proton conduction and pumping in the PM, from intracellular to extracellular space. For the first time a complex cellular reaction in a bionanodevice can be accounted for in full atomic detail in its complete native environment (full article, .5 MBytes).
Purple bacteria, like plants, fuel their metabolism with light energy and have developed for this purpose an efficient apparatus for harvesting sunlight, the PSU, key features of which had been conceptually established long ago (introductory movie, 25 MBytes). The atomic structure of all of its components have been solved, some only recently: the photosynthetic reaction center, the light harvesting complexes LH-I and LH-II, and the bc1 complex that work together to absorb light and pump protons vectorially across the membrane, as well as the ATPase, that lets protons pass back converting their energy into synthesis of DNA. Our group has modeled in a series of studies during the past decade all individual protein components of the PSU and has pioneered simulations of large patches of membranes. We seek to eventually place all components into the integral bionanodevice and model it as it exists in the cell (full article, 8 Mbytes).