SIMULATIONS OF SUPRAMOLECULAR BIOLOGICAL STRUCTURES

超分子生物结构的模拟

• 批准号: 8364241
• 负责人: Klaus Schulten
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364241
• 关键词: Biological; Biomedical Research; Cell Shape; Cell physiology; Cells; Cellular Membrane; Collaborations; Cytoplasm; Data; Electron Microscopy; Funding; Genetic Transcription; Grant; High Performance Computing; Integral Membrane Protein; Membrane Proteins; Methods; Molecular; National Center for Research Resources; Nuclear Pore; Nucleoplasm; Organism; Pore Proteins; Principal Investigator; Process; Protein Export Pathway; Proteins; Research; Research Infrastructure; Resolution; Resources; Ribosomes; Source; Structure; System; Techniques; Time; United States National Institutes of Health; cost; ds-DNA; flexibility; helicase; molecular dynamics; programs; protein complex; protein folding; protein function; research study; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We propose to investigate the organization and function of proteins and protein complexes within cells in order to elucidate how atomic-scale dynamics drives large-scale cellular processes. For our studies, we employ the highly efficient molecular dynamics (MD) program NAMD, developed in our lab, to carry out large-size and long-time simulations of seven key processes taking place in nearly all cellular organisms. MD affords a simultaneous resolution in both time and space for the study of these processes unattainable by experimental techniques. With our recently developed MD Flexible Fitting method, we join MD and experiment, taking atomic-resolution, but unphysiological, crystal structures and fit them to lower resolution, but physiologically relevant, electron-microscopy data, yielding structures representing functional macro-molecular systems. Actually, all of our projects involve close collaboration with experimentalists. We propose to study (i) how proteins fold from an unfolded starting sequence, (ii) how proteins are synthesized by the ribosome and (iii) how nascent proteins are exported into cellular membranes or excreted. On a larger scale, we seek to study how cells shape their internal membranes, by proteins called (iv) BAR domains or by (v) integral membrane proteins. Lastly, we investigate key components of transcription in cells, (vi) helicases, that unwind double stranded DNA, and (vii) nuclear pore proteins that control export and import between a cells cytoplasm and nucleoplasm.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们建议研究细胞内蛋白质和蛋白质复合物的组织和功能，以阐明原子尺度动力学如何驱动大规模细胞过程。在我们的研究中，我们采用实验室开发的高效分子动力学 (MD) 程序 NAMD，对几乎所有细胞生物体中发生的七个关键过程进行大规模和长时间的模拟。 MD 为研究这些实验技术无法实现的过程提供了时间和空间上的同步分辨率。通过我们最近开发的 MD 灵活拟合方法，我们将 MD 和实验结合起来，采用原子分辨率但非生理性的晶体结构，并将其拟合到分辨率较低但生理相关的电子显微镜数据，产生代表功能性大分子系统的结构。事实上，我们所有的项目都涉及与实验学家的密切合作。我们建议研究（i）蛋白质如何从展开的起始序列折叠，（ii）核糖体如何合成蛋白质以及（iii）新生蛋白质如何输出到细胞膜或排泄。在更大范围内，我们寻求研究细胞如何通过称为 (iv) BAR 结构域的蛋白质或 (v) 整合膜蛋白来塑造其内膜。最后，我们研究了细胞转录的关键成分，(vi) 解旋双链 DNA 的解旋酶，以及 (vii) 控制细胞质和核质之间输出和输入的核孔蛋白。