Wet Electrostatics and Biomolecular Self-Assembly

近年来，在理解具有单一电荷符号的带电聚合物（如DNA）的行为方面取得了很大进展，这些聚合物表现出反直觉的行为，如像电荷吸引。目前的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，这些聚合物包括大多数蛋白质的一般带电聚合物。非弹性同步加速器x射线散射将用于研究介导这些聚合物之间相互作用的移动离子。实验还将集中在简单几何物体之间的原型相互作用上，比如带电荷的棒和片（例如DNA和膜），或者带相反电荷的棒和球（例如不同形状的蛋白质）在不同价盐的存在下。特别是，分子生物学技术将被用于设计具有电荷和大小的蛋白质突变体，这些突变体可以在这些研究中独立变化。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结合并使净带正电的抗生素蛋白失活。对这些影响的了解也可能导致改进水净化过程的方法。拟议工作的多学科性质为这个新兴的多学科领域所需的新型混合科学家提供了充足的教育机会。近年来，在理解具有单电荷符号的带电聚合物的行为方面取得了很大进展，这些聚合物表现出反直觉的行为，如类电荷吸引。目前的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，这些聚合物包括大多数蛋白质的一般带电聚合物。实验将集中在简单几何物体之间相互作用的原型例子上，比如带同种电荷的棒和片（例如DNA和膜），或者带相反电荷的棒和球（例如不同形状的蛋白质）在盐的存在下。特别是，最先进的分子生物学技术将用于这些研究中具有明确定义的电荷和大小的工程蛋白突变体。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结合并使净带正电的抗生素蛋白失活，从而导致长期感染。对这些静电效应的理解也可能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个新兴的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.