SIMULATIONS OF SUPRAMOLECULAR BIOLOGICAL STRUCTURES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在2006/2007年间，我们小组共发表了41篇论文[1-41]，报道了我们的LRAC赠款使研究成为可能。在过去的15年里，我们发表了150多项在NSF中心实现的分子动力学(MD)研究，这些研究被引用了4000多次。我们研究的巨大影响归功于我们与实验的紧密联系：我们2006/2007年的论文中约有一半是与实验合作者共同撰写的。通过我们自己和其他人使用我们的程序NAMD进行的模拟，NSF高性能计算机的能力每天都被主流生命科学所利用。在过去的五年里，分配给我们的超级计算时间已经导致了无数的突破性项目，包括第一次模拟整个生命形式[39]，解决水通道蛋白的机制[42]，阐明lac抑制物-DNA复合体的结构动力学[43]，第一个发现重复蛋白的二级和三级弹性[6]，以及指导用于DNA测序的合成纳米孔的开发[44]。在过去的一年里，我们成功地完成了四个LRAC项目，涉及蛋白质气体传导[7，12，20，19，31]，机械敏感通道[11，30，33]，核运输因子[3，9，45]和重复蛋白的弹性[6]。在未来的一年里，我们将继续三个生物学前沿的项目(病毒感染、鞭毛运动和组装以及核糖体的蛋白质合成)，我们将推出五个雄心勃勃的新项目，这些项目已经取得了重大进展，但现在非常需要超级计算机的时间。这些项目涉及一种革命性的新算法，用于灵活地将晶体结构与电子显微镜密度相匹配，并在两个大小(通过组装整个细胞器，紫色细菌的色团)以及在时间(通过监测光反应LOV结构域蛋白质的1微秒动态)方面突破MD的极限，后者是通过对我们的软件NAMD进行的针对小型系统的革命性多处理器缩放改进而实现的。最后，我们还研究了与肌肉伸展和血液凝结有关的蛋白质，以及塑造细胞内膜形状的蛋白质。

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.