MODELING MOTOR PROTEINS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们用分子动力学模拟方法研究了肌动蛋白的X射线结构性质。肌动蛋白只有在防止聚合的生化修饰之后才能结晶。这就提出了这样一个问题：从X射线结构推断出的性质是否反映了肌动蛋白的真实性质，还是仅仅反映了修饰后的蛋白质的性质。加州大学旧金山分校计算机图形实验室的支持对于可视化和解释我们的分子动力学模拟结果是必不可少的。我们的结果表明，在许多情况下，修饰蛋白的行为与天然肌动蛋白不同。肌动蛋白由四个亚域组成，重要的是能够通过图形操作这些亚域之间的空间关系来生成新的假定肌动蛋白结构。此外，这个项目还包括研究被认为有助于调节肌球蛋白功能的阿尔法螺旋螺旋结构域的热力学稳定性。分子动力学模拟的结果需要图形可视化软件的广泛使用。

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. We have used molecular dynamics simulations to investigate the properties of x-ray structures of actin. Actin can only be crystalized following biochemical modification that prevents polymerization. This raises the question as to whether properties deduced from the x-ray structures reflect the true properties of actin, or only of modified proteins. The support of the Computer Graphics Laboratory at UCSF is essential for visualization and interpretation of the results of our molecular dynamics simulations. Our results indicate that in many cases, the modified proteins behave differently from native actin. Actin is comprised of four subdomains, and it is important to be able to generate new putative actin structures by graphical manipulation of the spatial relationships between these sub-domains. Additionally, this project involves investigating the thermodynamic stability of putative alpha-helical coiled-coil domains that have been postulated to help regulate myosin function. The results of molecular dynamics simulations require extensive use of the graphical visualization software.