Wet Electrostatics and Biomolecular Self-Assembly

近年来，在理解具有单个电荷符号的带电聚合物（例如DNA）的行为方面取得了很大进展，这些聚合物表现出违反直觉的行为，例如类电荷吸引。本项目旨在将这种理解扩展到具有正电荷和负电荷的聚合物，这些聚合物包括包括大多数蛋白质的一般带电聚合物。非弹性同步辐射X射线散射将被用来研究介导这些聚合物之间相互作用的移动的离子。实验还将集中在简单的几何物体之间的原型相互作用，如带电的杆和片（例如。DNA和膜），或带相反电荷的棒和球（例如，不同形状的蛋白质）。特别是，分子生物学技术将用于工程蛋白质突变体的电荷和大小，可以独立地改变这些研究。这项工作可能会导致囊性纤维化的新治疗策略，其中带负电荷的聚合物如F-肌动蛋白和DNA结合并结合带正电荷的抗生素蛋白。了解这些影响也可能导致水净化过程的改进方法。多学科性质的拟议工作提供了充分的教育机会，为新的混合科学家在这个新兴的多学科领域所必需的。近年来，在理解带电聚合物的行为与一个单一的符号的电荷，这表现出违反直觉的行为，如类电荷的吸引力已经取得了很大进展。本项目旨在将这种理解扩展到具有大量正电荷和负电荷的聚合物，这些聚合物包括包括大多数蛋白质在内的一类带电聚合物。实验将集中在简单的几何物体之间的相互作用的典型例子，如带电的杆和片（例如。DNA和膜），或带相反电荷的棒和球（例如，不同形状的蛋白质）。特别是，国家的最先进的分子生物学技术将用于工程蛋白突变体与明确定义的电荷和大小，这些研究。这项工作可能会导致囊性纤维化的新治疗策略，其中带负电荷的聚合物如F-肌动蛋白和DNA结合并结合带正电荷的抗生素蛋白，从而导致长期感染。对这些静电效应的理解也将潜在地导致水净化过程的改进方法。拟议工作的多学科性质将为这一新兴多学科领域所需的新型混合科学家提供充足的教育机会。

In recent years, much progress has been made in understanding the behavior of charged polymers with a single sign of charge (such as DNA), which exhibit counterintuitive behavior such as like-charge attraction. The present project aims to extend this understanding to polymers with both positive and negative charges, which comprise a general class of charged polymers that includes most proteins. Inelastic synchrotron x-ray scattering will be employed to study the mobile ions that mediate interactions between these polymers. Experiments will also concentrate on archetypal interactions between simple geometric objects, such as like-charged rods and sheets (ex. DNA and membranes), or oppositely charged rods and spheres (ex. proteins of different shapes) in the presence of salts with different valences. In particular, molecular biology techniques will be used to engineer protein mutants with charges and sizes that can be independently varied for these studies. This work may lead to new therapeutic strategies for cystic fibrosis, where negatively charged polymers such as F-actin and DNA bind to and inactivate net positively charged antibiotic proteins. An understanding of these effects may also lead to improved methods of water purification processes. The multi-disciplinary nature of the proposed work provides ample educational opportunities for the new kind of hybrid scientists necessary in this emerging multidisciplinary field.In recent years, much progress has been made in understanding the behavior of charged polymers with a single sign of charge, which exhibit counterintuitive behavior such as like-charge attraction. The present project aims to extend this understanding to polymers with large numbers of both positive and negative charges, which comprise a general class of charged polymers that includes most proteins. Experiments will concentrate on archetypal examples of interactions between simple geometric objects, such as like-charged rods and sheets (ex. DNA and membranes), or oppositely-charged rods and spheres (ex. proteins of different shapes) in the presence of salts. In particular, state-of-the-art molecular biology techniques will be used to engineer protein mutants with well-defined charges and sizes for these studies. This work may lead to new therapeutic strategies for cystic fibrosis, where negatively charged polymers such as F-actin and DNA bind to and inactivate net positively charged antibiotic proteins, and thereby contribute to long-term infections. An understanding of these electrostatic effects will also potentially lead to improved methods of water purification processes. The multi-disciplinary nature of the proposed work will provide ample educational opportunities for the new kind of hybrid scientists necessary in this emerging multidisciplinary field.