EXPERIMENTAL AND COMPUTATIONAL METHODOLOGIES FOR BIOMATERIALS CHARACTERIZATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们提出了一种将最先进的计算和实验固态相结合的综合方法 新型多肽和蛋白质纳米级结构和动力学的核磁共振表征方法 生物材料。这种方法旨在克服更传统的光谱技术的局限性。 以及显微技术在生物材料分析中的应用。具体地说，我们将开发固态 基于核磁共振的多肽大分子结构、动力学和交联性表征方法 水凝胶组件。我们将继续开发和改进可极化或非相加的力 基于统计力学的多肽和多肽溶剂模型化方法的适用领域 (水)相互作用。我们将建立可极化(非加性)表征的协议 用从头算方法预测小肽和氨基酸的相对溶剂化自由能 类似物；使用极化力场进行有效自由能计算的方法。我们的初步工作将 重点是施耐德和波昌开发的多肽水凝胶(子项目2)。多肽水凝胶是 有望用于肝组织再生的支架材料。这些材料代表了 固体核磁共振实验及结构和动力学计算方法的发展 非晶态多肽和蛋白质材料的分析 宏观和中观尺度，但没有详细的结构和动力学信息。 获取原子级结构信息是非常必要的，因为它将指导下一个 为临床应用开发性能可调的新一代水凝胶材料。我们将描述 多肽水凝胶的侧面和侧面组装，解决其骨架和侧链动力学，以及探针 水在运动。建立在水凝胶上的实验和计算方法将是 一般适用于(但不限于)在以下领域开发的各种多肽和蛋白质生物材料的研究 这个科布雷计划的其他子项目。在更广泛的意义上，我们预计我们的方法将有益于 整个生物材料社区，因为它解决了当前对新的原子尺度解析方法的需求 能够探测通过传统结构技术难以解决的复杂的非晶态生物材料。

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.