RECONSTRUCTING PROTEINS FROM CHEMICAL SHIFT INFORMATION

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。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。 从蛋白质的骨架扭转角度重建蛋白质的三维结构是一个持续的挑战，因为这些角度的微小误差会产生结构上的重大错误。在此背景下，我们正在进行一项计算实验，以评估是否可以从高度近似的骨架扭转角确定蛋白质构象，这种信息现在很容易从NMR中获得。具体地说，骨架扭转角取自已知结构的蛋白质，并映射到60 x 60的网格正方形中，称为中间态。侧链原子超出了？-碳被丢弃。然后使用蛋白质骨架的介态表示从介态五聚体的片段文库中提取可能的候选物，然后通过基于Monte Carlo的片段组装模拟来鉴定与给定的介态序列相容的稳定构象。仅使用三个简单的能量项来衡量稳定性：分子压实、软球排斥和氢键。初步结果发表在：1。龚海鹏、帕特里克J.弗莱明和乔治D. Rose（2005）从高度近似的骨架扭转角构建天然蛋白质构象。Proc Nat. Acad.科学，102：16227-16232。2.帕特里克J.弗莱明，龚海鹏和乔治D. Rose（2006）Secondary structure determines protein topology.蛋白质科学（加速出版），出版中。我们现在准备通过对更大的代表性蛋白质选择进行许多模拟来测试这些想法。

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. Reconstructing a protein in three-dimensions from its backbone torsion angles is an ongoing challenge because minor inaccuracies in these angles produce major errors in the structure. Against this background, we are conducting a computational experiment to assess whether protein conformation can be determined from highly approximate backbone torsion angles, the kind of information that is now obtained readily from NMR. Specifically, backbone torsion angles are taken from proteins of known structure and mapped into 60 x 60 grid squares, called mesostates. Sidechain atoms beyond the ?-carbon are discarded. A mesostate representation of the protein backbone is then used to extract likely candidates from a fragment library of mesostate pentamers, followed by Monte Carlo-based fragment-assembly simulations to identify stable conformations compatible with the given mesostate sequence. Only three simple energy terms were used to gauge stability: molecular compaction, soft-sphere repulsion, and hydrogen-bonding. Initial results have been published in: 1. Haipeng Gong, Patrick J. Fleming and George D. Rose (2005) Building native protein conformation from highly approximate backbone torsion angles. Proc Nat. Acad. Sci., 102: 16227-16232. 2. Patrick J. Fleming, Haipeng Gong, and George D. Rose (2006) Secondary structure determines protein topology. Protein Science (accelerated publication), in press. We are now ready to put these ideas to the test by doing many simulations for a larger representative selection of proteins.