Membrane Protein Stability

项目摘要 了解蛋白质如何折叠是生物学的核心探索。研究了50多年 多年来，对可溶性蛋白质折叠的研究已经被证明对于解剖 多种疾病的分子基础。通过比较，膜的折叠研究 蛋白质(MPS)远远落后。从可溶性蛋白质研究中获得的知识 不能简单地转移到关于MPS的推断上，因为它们的溶剂是 不一样。编码嵌入在脂质双层中的MP的力量平衡必须是 不同于水中可溶蛋白质的。 我们的研究努力有助于填补这一关键空白，了解 膜蛋白的物理化学。我们将通过实验来确定能量 沿急剧变化的极性梯度稳定膜蛋白的作用力 磷脂双层界面。这些努力将得到分子的补充 模拟和数学系统建模。此外，我们的目标是将小说 向我们的工具箱提供技术，以解决主链氢的能量重要性 跨膜蛋白中的键。 我们的成果通过对以下方面的贡献在整个领域产生了广泛的影响 用于训练计算算法的信息数据库及其 掺入细胞催化蛋白质折叠的物理机制 机器。

Project Summary Understanding how proteins fold is a central quest in biology. Studied for over 50 years, investigations of soluble protein folding have proven invaluable for dissecting the molecular basis of a multitude of diseases. By comparison, folding studies of membrane proteins (MPs) lag far behind. The knowledge gained from soluble protein studies cannot simply be transferred to inferences about MPs because their solvents are different. The balance of forces encoding a MP embedded in a lipid bilayer must be distinct from that of soluble proteins in water. Our research efforts contribute to filling this key gap in the understanding the physical chemistry of membrane proteins. We will experimentally determine of energetic forces stabilizing membrane proteins along the steeply changing polarity gradient of the phospholipid bilayer interface. These efforts will be complemented by molecular simulations and mathematic systems modeling. In addition, we aim to incorporate novel techniques to our toolbox to address the energetic importance of backbone hydrogen bonds in transmembrane proteins. Our results have broad ranging impact in the field at large through contributions to information databases used in training computational algorithms and by their incorporation in physically realistic mechanisms for protein folding catalysis by cellular machines.