SIMULATIONS OF SUPRAMOLECULAR BIOLOGICAL STRUCTURES

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During 2006/2007, our group published a total of 41 papers [1-41] reporting on research made possible by our LRAC grant. Over the past 15 years, we have published more than 150 molecular dynamics (MD) studies realized at NSF centers, which were cited over 4,000 times. The great impact of our research is due to our tight connection with experiment: about half of our 2006/2007 papers were co-authored with experimental collaborators. Through both our own simulations and those of others using our program NAMD, the power of NSFs high performance computers is being harnessed daily for mainstream life science. In the past five years, the supercomputing time allocated to us has resulted in numerous breakthrough projects, including the first simulation of an entire life form [39], solving the mechanism of aquaporins [42], elucidating the structural dynamics of the lac repressor-DNA complex [43], being the first to discover the secondary and tertiary elasticity of repeat proteins [6], and guiding the development of synthetic nanopores for DNA sequencing [44]. Over the last year, we have successfully completed four LRAC projects addressing protein gas conduction [7,12,20,19,31], mechanosensitive channels [11,30,33], nuclear transport factors [3,9,45], and elasticity of repeat proteins [6]. In the coming year, we will continue three projects at the forefront of biology (virus infection, flagellum motility and assembly, and protein synthesis by the ribosome) and we are introducing five ambitious, new projects for which significant progress has already been made, but which are now in great need of supercomputer time. These projects involve a revolutionary new algorithm for flexibly fitting crystallographic structures to electron microscopy densities and push the limits of MD in both size (with the assembly of an entire organelle, the chromatophore of purple bacteria), as well as in time (with monitoring the 1 microsecond dynamics of photoreactive LOV-domain proteins), the latter feat made possible by revolutionary multiprocessor scaling improvements for small systems made to our software NAMD. Finally, we also examine proteins involved in muscle extension and blood clotting as well as proteins sculpting the shapes of inner-cellular membranes.