DE NOVO DESIGN OF A BETA SHEET PROTEIN

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。 我们使用计算和实验相结合的方法来设计蛋白质。我们所有项目的核心是用于蛋白质建模的Rosetta计划。通过与来自多所大学的开发人员合作，我们不断向Rosetta添加新功能，并在新问题上对其进行测试。作为SDSC战略应用合作的一部分，我们将研究Beta-Sheet蛋白质的从头设计。尽管自然界中有大量的全β蛋白质，但蛋白质设计者一直未能对β-折叠蛋白质进行从头设计。为了创造一种全新的贝塔蛋白，我们使用了一种在结构优化和序列优化之间迭代的方案。我们的初步结果表明，我们能够合成以β-折叠为主的蛋白质作为二级结构。但它不是单体形式。一个可能的原因是我们没有采集足够的构象样本。这将需要大量的CPU时间。这就是为什么我们想要尝试使用TeraGrid超级计算机中心来进行更广泛的建模。

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 use a combination of computational and experimental methods to design proteins. Central to all of our projects is the Rosetta program for protein modeling. In collaboration with developers from a variety of universities, we are continually adding new features to Rosetta as well as testing it on new problems. As part of an SDSC Strategic Applications Collaboration, we will look at de novo design of beta-sheet proteins. Despite the large number of all-beta proteins in nature, the de novo design of a beta-sheet protein has eluded protein designers. To create a totally novel beta-protein we are using a protocol that iterates between structure refinement and sequence optimization. Our preliminary results showed that we are able to synthesize a protein of mainly beta sheet as the secondary structure. But its not in a monomeric form. One possible reason is that we didnt sample enough conformations. This will require a lot of CPU time. Thats why we want to try out the TeraGrid supercomputer center to do more extensive modeling.