MODELING MOTOR PROTEINS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们已经使用分子动力学模拟研究肌动蛋白的X射线结构的性质。肌动蛋白只能在阻止聚合的生化修饰后结晶。这就提出了一个问题：从X射线结构推导出的特性是否反映了肌动蛋白的真实特性，或者仅反映了修饰蛋白质的真实特性。加州大学旧金山分校计算机图形实验室的支持对于我们的分子动力学模拟结果的可视化和解释至关重要。我们的研究结果表明，在许多情况下，修饰的蛋白质的行为不同于天然肌动蛋白。肌动蛋白由四个子域组成，重要的是能够通过图形操作这些子域之间的空间关系来生成新的推定的肌动蛋白结构。此外，该项目还涉及研究假定的α-螺旋卷曲螺旋结构域的热力学稳定性，这些结构域被认为有助于调节肌球蛋白功能。分子动力学模拟的结果需要大量使用图形可视化软件。

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.