Flow enhanced protein crystallization at the air/water interface

CBET-0755968 Hirsa描述和使用蛋白质结构的能力使新药和药理学试剂的合理设计成为可能。通过对蛋白质和核酸的详细结构研究，在分子水平上理解生物系统方面取得了许多进展。然而，蛋白质必须首先结晶，才能使用对其结构进行精确描述的技术。与大量生长蛋白质晶体相比，2D蛋白质结晶大大简化了蛋白质研究的理论和实验方面。例如，2D系统不受重力的影响，这是一个困扰结晶学家的问题，没有负担得起的补救措施。在空气/水界面的二维蛋白质结晶需要蛋白质与含有配体的脂单分子层的特定结合。蛋白质链霉亲和素在溶液中已经在空气/水界面成功结晶，在那里已经铺展了含有配体生物素的脂单分子层。链霉亲和素和生物素之间的强亲和力在合适的条件下启动了界面上的晶体形成。PIS将研究由固定的开口圆柱体组成的系统中流动的影响，该系统由不断旋转的地板驱动，在很大范围的雷诺数范围内处于轴对称流动状态。PI们最近发现，S被流动剪切的界面可以在原本不会发生的条件下诱导结晶。PI发现，流动还可以产生一种新的晶体形式，其中蛋白质分子似乎以线性阵列的形式堆积在一起，类似于纳米线，但要长得多，而且完全笔直。PI计划研究与这些新晶体相关的大尺度流动现象。PI预计，改变雷诺数将分别调节成核速率和生长，这对结晶学家来说是一个挑战。有大量的蛋白质还没有通过传统的方法成功结晶，如果流动诱导结晶能够提高产率，那么这里的努力将是巨大的成功。多学科高级团队(来自机械工程和应用数学)，凭借其卓有成效的合作记录，将提供一个极好的机会，在一个令人兴奋的新兴领域--流体力学和蛋白质研究--教育研究生和本科生。

CBET-0755968HirsaThe ability to describe and use protein structure has enabled the rational design of new drugs and pharmacological agents. Many advances in understanding of biological systems at the molecular level have been made possible through detailed structural studies of proteins and nucleic acids. However, proteins must first be crystallized to use techniques that yield a precise description of their structure. In contrast to growing protein crystals in the bulk, 2D protein crystallization greatly simplifies both the theoretical and experimental aspects of protein studies. For example, 2D systems are not affected by gravity, an issue that plagues crystallographers with no affordable remedy. Two-dimensional protein crystallization at the air/water interface entails the specific binding of a protein to a lipid monolayer containing a ligand. The protein streptavidin, in solution, has been successfully crystallized at the air/water interface where a lipid monolayer containing a ligand, biotin, has been spread. The strong affinity between streptavidin and biotin initiates crystal formation at the interface under suitable conditions. The PIs will investigate the effects of flow in a system consisting of a stationary open cylinder driven by the constant rotation of the floor, in the axisymmetric flow regime over a wide range of Reynolds numbers. The PIs have recently discovered interface s sheared by flow can induce crystallization under conditions where none would otherwise occur. The PIs have discovered that flow can also produce a new form of crystal where the protein molecules appear to pack in a linear array, analogous to nano-wires, but much longer and perfectly straight. The PIs plan to investigate the macroscale flow phenomena associated with these new crystals. The PIs expect that varying the Reynolds number will regulate the nucleation rate and growth separately, which is a challenge for crystallographers. There are a vast number of proteins that have not been successfully crystallized by conventional means, and if flow-induced crystallization can improve the yield, then the effort here would be a resounding success. The multidisciplinary senior team (from mechanical engineering and applied mathematics), with its strong record of productive collaboration, will provide an excellent opportunity to educate graduate and undergraduate students in an exciting emerging field coupling hydrodynamics and protein studies.