The Free Energy Landscape of a Beta-Clamshell Protein

描述：（由申请人提供）蛋白质折叠问题是直接的 由于折叠不当引起的致病作用而具有医学相关性 蛋白质在各种癌症和疾病，如阿尔茨海默氏症， 克雅氏病构象或折叠自由能景观 一个小的β-蛤壳蛋白将通过检查其最 有趣的和相关的功能：天然的，变性的，过渡态， 中级合奏。由于这些分子的构象异质性， 合奏，理论和实验的协同方法是必需的， 充分描述能源景观。能量的定量描述 景观将产生和动力学的折叠过程上的 景观将被计算并与实验动力学数据进行比较。全 小β-蛤壳折叠的动力学和热力学图像 蛋白质将由此产生。

DESCRIPTION: (provided by applicant) The protein folding problem is of direct medical relevance due to the pathogenic effects caused by improperly folded proteins in various cancers and in diseases such as Alzheimer's and Creutzveldt-Jakob disease. The conformational or folding free energy landscape of a small beta-clamshell protein will be characterized by examining its most interesting and relevant features: the native, denatured, transition state, and intermediate ensembles. Due to the conformational heterogeneity of these ensembles, a synergistic approach of both theory and experiment is required to fully characterize the energy landscape. A quantitative picture of the energy landscape will be generated and the kinetics of the folding process on the landscape will be computed and compared to experimental kinetic data. A full kinetic and thermodynamic picture of the folding of a small beta-clamshell protein will thus be generated.