MOLECULAR STRUCTURE OF OLIGONUCLEOTIDES

描述(摘自申请人的摘要)：蛋白质折叠是一种 在生物化学中具有重要意义的问题。预测的能力 蛋白质一级序列中的蛋白质结构和功能 将对基于蛋白质的发展具有重要意义 制药公司。类似的，知识的实际机制，通过 蛋白质折叠，可以更好地理解分子 并允许设计避免疾病的蛋白质药物 折叠式陷阱。 已经了解了许多关于如何在原始状态下 蛋白质稳定了它的三维结构。然而，更不用说 了解蛋白质折叠平衡的另一半， 变性状态。核磁共振研究揭示了一些 这种状态的结构属性。然而，人们对此知之甚少 松散结构变化与自由能的关系 已定义状态。这个实验室最近开发了一种方法 评估突变引起的变性状态自由能变化。这个 方法涉及组氨酸-血红素结合强度的测定 在变性的iso-1-细胞色素c中连接。 该技术将用于： 评估义齿ISO-1随机线圈性能的偏差 细胞色素c与组氨酸在序列中的不同位置 关于亚铁血红素。 评估第二个站点变异的影响，包括近距离和远距离 由负责组氨酸-亚铁血红素连接的组氨酸变性 ISO-1-细胞色素c. 使用小的血红素多肽来评估局部和长期对 变性状态稳定性。 评价变性态自由能与变性剂的关系 集中精神。 这组实验将提供关于 变性蛋白质的能量景观，这将是非常有意义的 在定义蛋白质折叠方面的重要性。

DESCRIPTION (Adapted from applicant's abstract): Protein folding is a problem of great significance in biochemistry. The ability to predict protein structure and function from the primary sequence of a protein would be of great importance to the development of protein-based pharmaceuticals. Similar, knowledge of the actual mechanism by which proteins fold, could lead to a better understanding of molecular diseases and allow the design of protein pharmaceuticals which avoid folding traps. Much has been learned about how interactions in the native state of a protein stabilize its three-dimensional structure. However, much less is understood about the other half of the protein folding equilibrium, the denatured state. NMR studies have shed light on some of the structural properties of this state. However, little is known about the relationship between structural changes and free energy in this loosely defined state. This laboratory has recently developed a means of assessing mutation-induced denatured stated free energy changes. The method involves measurement of in the bond strength of histidine-heme ligation in denatured iso-1-cytochrome c. In this proposal, this technique will be used to: evaluate deviations in random coil behavior for denture iso-1- cytochromes c with histidine at different positions in t he sequence with respect to the heme. evaluate the consequences of second site variants both near to and far from the histidine responsible for histidine-heme ligation in denatured iso-1-cytochrome c. use small heme-peptides to evaluate local versus long-range effects on denatured state stability. assess the dependence of denatured state free energy on denaturant concentration. This set of experiments will provide much needed knowledge about the energy landscapes of denatured proteins, which will be of great importance in defining the protein folding.