Forces Driving Membrane Protein Folds

项目摘要 了解蛋白质如何折叠是生物学的核心任务。学习超过50年 多年来，可溶性蛋白质折叠的研究已被证明是非常宝贵的解剖， 许多疾病的分子基础。相比之下，膜的折叠研究 蛋白质远远落后。从可溶性蛋白质研究中获得的知识不能简单地 因为它们的溶剂不同，所以可以转移到推论上。余额 编码包埋在脂质双层中的MP的力必须与可溶性MP的力不同。 水中的蛋白质 我们的研究工作有助于填补这一关键空白，了解物理 膜蛋白化学我们将通过实验来确定 稳定膜蛋白沿着急剧变化的极性梯度， 磷脂双层界面，量化骨架氢键强度，并扩展 我们的膜蛋白折叠模型库，包括那些与a-螺旋 二级结构这些努力将得到分子模拟的补充， 根据需要进行其他溶液生物物理学询问。 我们的研究结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， 在蛋白质折叠催化的物理现实机制中， 机械.

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 lag far behind. The knowledge gained from soluble protein studies cannot simply be transferred to inferences about 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, quantify backbone hydrogen bond strengths, and expand our repertoire of membrane protein folding models to include those with an a-helical secondary structure. These efforts will be complemented by molecular simulations and other solution biophysics interrogations as needed. 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.