A Spectroscopic and Computational Structure-Function Study of Biosilicification Peptides

金属氧化物包括氧化硅（SiO2，二氧化硅）和氧化钛（TiO2，二氧化钛）有许多应用，如绝缘体，纺织涂料，催化剂，化学去污剂，太阳能电池组件，医疗/牙科植入物和化学传感器。这些重要硬材料的工业合成和形态控制需要极端的温度、压力和pH值，因此需要大量的能量。相比之下，生物有机体通过精确控制形态完成了令人印象深刻的矿物氧化物生产壮举，这几乎是工业方法所无法比拟的，并且在环境温度，压力和生理pH值下进行，这一过程被称为生物矿化。硅藻是一种海洋微藻，其特征是由有机物质和二氧化硅组成的复杂装饰的细胞壁。硅藻吸收溶解形式的硅，并将其转化为精细的二氧化硅结构，这一过程迄今尚不清楚，蛋白质和其他有机聚合物被认为在二氧化硅形成的催化剂和模板中起着重要作用。这项研究旨在了解硅藻用来形成二氧化硅的蛋白质所起的特定作用，其直接目标是制造更小、更便宜的分子，模仿硅藻在温和条件下控制二氧化硅形成的能力。长期目标是使用类似设计的小分子来控制非生物氧化物如TiO2的形成。该项目将为年轻的科学家和工程师提供使用光谱和计算技术来阐明生物材料结构-功能关系的培训。该研究将利用固态核磁共振（ssNMR）、先进的非平衡分子动力学（MD）计算和新的化学合成技术，来确定天然存在的肽的分子结构特性和相互作用，这些相互作用是硅化活性的基础。最初的研究将集中在R5肽的修饰和未修饰形式上，R5肽是从硅藻物种圆柱形藻的生物硅化蛋白silaffin中提取的。本研究项目将解决的具体问题包括：1。未经修饰的硅化肽域衍生物（如R5）是否具有促进肽-肽相互作用的特定二级结构，从而导致高阶结构的形成？2. 肽-二氧化硅相互作用的本质是什么？3. 氨基酸修饰如何影响二氧化硅中的肽结构和肽-肽相互作用，最重要的是，这些修饰如何影响肽-二氧化硅相互作用？4. R5可以诱导二氧化硅的形成，也可以诱导非生物氧化物如TiO2的形成。R5用来形成二氧化硅的结构原理与它用来形成其他氧化物的原理相似吗？这些问题的答案将为多肽和其他小分子的设计提供基于结构的原则，这些小分子可以在体外模拟天然存在的蛋白质（如硅蛋白）的硅化活性。

Metal oxides including silicon oxide (SiO2, silica) and titanium oxide (TiO2, titania) have numerous applications as insulators, textile coatings, catalysts, chemical decontaminants, solar cell components, medical/dental implants and chemical sensors. Industrial synthesis and morphological control of these important hard materials requires extremes in temperature, pressure and pH and are thus energetically demanding. In contrast, biological organisms accomplish impressive feats of mineral oxide production with precise control over morphology that is virtually unmatched by industrial approaches, and do so at ambient temperature, pressure and at physiological pH in a process called biomineralization. Biogenic silica (i.e. biosilica) is produced in gigaton quantities annually by the diatom, a marine microalgae characterized by an intricately decorated cell wall that is composed of organic material and silica. Diatoms take in silicon in dissolved form, and convert it to elaborate silica structures, in an as yet poorly understood process where proteins and other organic polymers are believed play important roles as catalysts and templates for silica formation. This research is aimed at understanding the specific roles played by proteins that are used by diatoms to form silica, with the immediate goal of making smaller, and less expensive molecules that imitate the diatom's ability to control silica formation under mild conditions. The long-term goal is to use similarly designed small molecules to effect the controlled formation of non-biological oxides like TiO2. This project will provide training for young scientists and engineers in the use of spectroscopic and computational techniques to elucidate structure-function relationships in biomaterials.The research will utilize solid state NMR (ssNMR), advanced non-equilibrium molecular dynamics (MD) computations, and novel chemical synthesis techniques, to determine the molecular structural properties and interactions that underlie the silicifying activities of naturally-occurring peptides. Initial study will be focused on modified and unmodified forms of the R5 peptide, derived from the bio-silicification protein silaffin of the diatom species Cylindrotheca fusiformis. Specific questions that this research project will address include: 1. Do unmodified silicifying peptide domain derived (e.g. R5) assume specific secondary structures that promote peptide-peptide interactions which in turn lead to formation of higher order structures? 2. What is the nature of peptide-silica interactions? 3. How do amino acid modifications influence peptide structure and peptide-peptide interactions in silica, and, most importantly, how do these modifications affect peptide-silica interactions? 4. Can R5, that induce silica formation, also induce formation of non-biological oxides like TiO2. Are the structural principles used by R5 to form silica similar to the principles it uses to form other oxides? Answers to these questions will provide structure-based principles for the design of peptides and other small molecules that can mimic in vitro the silicifying activities of naturally occurring proteins like silaffin.