"Understanding, engineering and exploiting protein self-assembly."

在许多生物环境中，蛋白质形成纤维是必需的。尽管如此，蛋白质可复制形成具有特定大小、形状和化学特征的纤维的方式仍然难以捉摸。事实上，大自然很可能进化出了许多不同的方法来回答这个问题。这项发现拨款将建立对从可溶于水的分离蛋白质到具有显著不同性质的纤维形式的转变的理解。通过这样做，将发展对这些关键生物实体的基本见解，我们将能够为新的目的调整和优化蛋白质原纤维。这项发现奖助金针对两种特定类型的蛋白质纤维。 第一种是蜘蛛丝，这种材料的强度和韧性在目前的合成材料中找不到。我们正在使用细菌来生产蜘蛛用来包裹猎物的丝类，这有双重优势，一是允许我们随意修改单个氨基酸，二是可以结合各种形式的原子，从而可以使用核磁共振(核磁共振)光谱。我们正在研究的第二类蛋白质是胶原蛋白。在这种情况下，我们正在使用计算方法来设计类胶原蛋白，这些蛋白部分是在细菌中制造的，部分是通过化学方法制造的。因为蛋白质的一部分是化学合成的，我们可以将更广泛的化学功能结合到这些蛋白质中。 在这两种情况下，我们使用核磁共振光谱来精确定位蛋白质中每个单独原子在溶液和纤维形式中的位置。我们还可以监测从可溶到纤维状转变过程中原子位置和运动的具体变化。在这样做的同时，我们监控使用原子力显微镜(AFM)形成的纤维的类型和特性。这使得在测量纤维强度和弹性的同时，可以直观地看到纤维表面。根据氨基酸序列的变化，通过比较原子位置和机械性能，我们可以设计出基于蜘蛛丝或胶原的新形式的纤维，但具有特定的工程特性。

Fibre formation by proteins is required in many biological situations. Despite this fact, the way that proteins reproducibly form fibres with specific size, shape and chemical features remains elusive. It is likely, in fact, that nature has evolved a number of different approaches to answer this problem. This Discovery Grant will build understanding of the transformation from isolated proteins soluble in water to fibrillar forms with dramatically different properties. By doing so, fundamental insight into these critical biological entities will be developed and we will be able to tweak and optimize protein fibrils for new purposes. Two specific types of protein fibre are targeted in this Discovery Grant. The first of these is spider silk, a material with strength and toughness not found in current synthetic materials. We are using bacteria to produce the type of silk that spiders use to wrap their prey, with the dual advantage of allowing us to modify individual amino acids at will and to incorporate forms of atoms allowing use of nuclear magnetic resonance (NMR) spectroscopy. The second class of protein we are studying is collagen. In this case, we are using computational methods to engineer collagen-like proteins that are made partially in bacteria and partially by chemical methods. Because parts of the protein are made chemically, we can incorporate a much wider variety of chemical functionality into these proteins. In both cases, we use NMR spectroscopy to pinpoint the locations of each individual atom within the protein both in solution and in fibre form. We can also monitor specific changes to atomic positions and motions during the transition from soluble to fibrous. As we do so, we monitor the types and properties of fibres that are formed using atomic force microscopy (AFM). This allows visualization of the fibre surface alongside measurement of strength and elasticity. Comparison of the atomic positioning to mechanical properties as a function of changes in amino acid sequence allows us to engineer new forms of fibre based on spider silk or collagen but with specific, engineered properties.