DE NOVO DESIGN OF A BETA SHEET PROTEIN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 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 研究中心，而研究中心不一定是研究者所在的机构。 我们使用计算和实验方法的组合来设计蛋白质。我们所有项目的核心是罗塞塔蛋白质建模计划。通过与来自不同大学的开发人员合作，我们不断为Rosetta添加新功能，并在新问题上进行测试。作为SDSC战略应用合作的一部分，我们将研究β折叠蛋白的从头设计。尽管自然界中存在大量的全β蛋白，但β折叠蛋白的从头设计一直困扰着蛋白质设计师。为了创造一种全新的β-蛋白质，我们使用了一种在结构优化和序列优化之间迭代的协议。我们的初步结果表明，我们能够合成一种主要以β折叠作为二级结构的蛋白质。但它不是单体形式。一个可能的原因是我们没有对足够的构象进行采样。这将需要大量的CPU时间。这就是为什么我们想尝试TeraGrid超级计算机中心来做更广泛的建模。

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.