NOVEL PARADIGM FOR LONG TIME PEPTIDE/PROTEIN DYNAMICS

我们将运用我们的新范式来处理柔性肽和蛋白质的长时间动力学，以描述几种生物系统的动力学，包括模型β -桶蛋白的展开。此外，我们将继续测试和提高蛋白质的适用性和效率。此外。我们将继续检验和提高理论的适用性和有效性。该理论旨在描述没有单一天然结构的肽的动力学，具有柔性部分的蛋白质，蛋白质结构域的相对运动以及蛋白质的展开。缺乏单一天然结构的肽的一个主要例子是淀粉样β -肽，它与阿尔茨海默病的斑块形成有关，它可能采用随机的线圈状、khi-螺旋状或β -片状结构（后者促进斑块形成）。该理论的目标是描述比分子动力学（MD）刺激更长的时间尺度上的动力学，描述比分子动力学刺激更长的时间尺度上的动力学。应用将考虑神经递质，如met-enkephalin和内皮素，它们与高血压、肾衰竭、心肌梗死等有关，以及β -桶蛋白的展开。将所有这些系统与MD模拟进行比较，将为理论提供明确的（无可调参数）测试，并使其得以改进。该理论将统计力学中简化描述的一般原理与溶剂动力学的流体动力学模型相结合，并对所有假设进行严格的检验和改进。计算将与Scherer（芝加哥）利用单分子光谱和飞秒红外泵-探针各向异性方法计划的肽动力学实验探针密切协调。我们还将预测核磁共振实验，特别是考虑不同核磁共振数据之间和/或核磁共振和x射线数据之间存在差异的情况。

We will apply our novel paradigm for treating the long time dynamics of flexible peptides and proteins to describe the dynamics of several biosystems, including the unfolding of a model beta-barrel protein. In addition, we will continue to test and enhance the applicability and efficiency of the protein. In addition. we will continue to test and enhance the applicability and efficiency of the theory. This theory is designed to describe the dynamics of peptides with no single native structure, proteins with flexible portions, relative motions of domains in proteins, and the unfolding of proteins. A primed example of a peptide lacking a single native structure is the amyloid beta-peptide, involved in plaque formation occurring with Alzheimer's disease, which may adopt random coil-, khi- helical, or beta-sheet structures (the latter promotes plaque formation). The goal of the theory is to describe dynamics of time scales orders of magnitude longer than those accessible to molecular describe dynamics on time scales orders of magnitude longer than those accessible to molecular dynamics (MD) stimulations. Applications will consider neurotransmitters, such as met-enkephalin, and endothelins which are associated with hypertension, renal failure, myocardial infarction, etc., and the unfolding of a beta-barrel protein. Comparisons with MD simulations for all these systems will provide unambiguous (no adjustable parameters) tests of the theory and will enable its refinement. The theory merges general principles of reduced descriptions in statistical mechanics with hydrodynamic models for the solvent dynamics, and with the scrupulous testing and improvement of all assumptions. Computations will be closely coordinated with planned experimental probes of peptide dynamics by Scherer (Chicago) using single molecule spectroscopy and femtosecond infrared pump-probe anisotropy methods. We will also predict NMR experiments and especially consider cases where discrepancies exist between different NMR data and/or between NMR and X-ray data.