EXPERIMENTAL AND COMPUTATIONAL METHODOLOGIES FOR BIOMATERIALS CHARACTERIZATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们提出了一个综合的方法，结合国家的最先进的计算和实验的固态 表征新型肽和蛋白质纳米级结构和动力学的NMR方法 生物材料。这种方法旨在克服更传统的光谱分析的局限性。 以及用于生物材料分析的显微技术。具体来说，我们将开发固态 用于表征肽中大分子结构、动力学和交联的基于NMR的方案 水凝胶组件。我们将继续发展和完善极化，或非加性，力 统计力学应用领域  肽-肽和肽溶剂建模的方法 （水）相互作用。我们将建立协议的特点极化（非添加剂） 小分子肽和氨基酸相对溶剂化自由能的从头计算力场 类似物;使用极化力场的有效自由能计算方法。我们的初步工作将 重点介绍Schneider和Pochan开发的肽水凝胶（子项目2）。肽水凝胶是 很有前途的肝组织再生支架。这些材料代表了理想的模型系统， 固体核磁共振实验和结构与动力学计算方法的发展 非结晶肽和蛋白质材料的分析，因为它们已经在 宏观和介观尺度，但详细的结构和动力学信息是不可用的。 获得原子级的结构信息是非常必要的，因为它将指导下一个 用于临床应用的具有可调性质的水凝胶材料。我们将描述 肽水凝胶横向和表面组装，解决其主链和侧链动力学，以及探针 水的运动。建立在水凝胶上的实验和计算方法将在 通常适用于（但不限于）研究开发的广泛的肽和蛋白质生物材料， COBRE计划的其他子项目。从更广泛的意义上说，我们希望我们的方法有利于 整个生物材料界，因为它解决了目前对新的原子尺度分辨率方法的需求 能够探测传统结构技术难以处理的复杂无定形生物材料。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose an integrated approach combining state-of-the-art computational and experimental solid-state NMR methodologies for characterization of nanoscale structure and dynamics of novel peptide and protein biomaterials. This approach is designed to overcome the limitations of the more traditional spectroscopic and microscopic techniques applied for analysis of biomaterials. Specifically, we will develop solid-state NMR based protocols for characterization of macromolecular structure, dynamics and cross-links in peptide hydrogel assemblies. We will continue development and refinement of polarizable, or non-additive, force fields applicable to statistical mechanics  based approaches for modeling peptide-peptide and peptidesolvent (water) interactions. We will establish protocols for the characterization of polarizable (non-additive) force fields through ab initio prediction of relative solvation free energetics of small peptides and amino acid analogues; methods for efficient free energy calculations using polarizable force fields. Our initial work will focus on peptide hydrogels developed by Schneider and Pochan (subproject 2). Peptide hydrogels are promising scaffolds for liver tissue regeneration. These materials represent ideal model systems for development of experimental solid-state NMR and computational methods for structure and dynamics analysis of noncrystalline peptide and protein materials as they have been extensively characterized on macroscopic and mesoscopic scales but detailed structure and dynamics information is not available. Gaining atomic-level structural information is critically needed as it will guide the design of the next generation hydrogel materials with tunable properties for clinical applications. We will characterize the lateral and facial assembly of peptide hydrogels, address their backbone and sidechain dynamics, and probe the water motions. The experimental and computational methodologies established on hydrogels will be generally suited (but not limited) to studies of a broad range of peptide and protein biomaterials developed in other subprojects of this COBRE program. In a broader sense, we expect our approach to be beneficial to the entire biomaterials community as it addresses the current need for new atomic-scale resolution methods capable of probing complex amorphous biomaterials intractable by conventional structural techniques.