RUI: Continuum Models of DNA and Protein Coils

Haverford College, Haverford PA

Investigators

Abstract

Manning The investigator and his students and colleagues study elastic rod models of biological molecules, including DNA and coiled-coil proteins. In the case of DNA, a classical rod model is enhanced by including intrinsic curvature, flexibility, and deformations imposed by protein-binding. Among other applications, this model is used to analyze cyclization experiments, which can probe DNA and protein structure and flexibility under biologically realistic solvent conditions. The large deformations imposed on DNA by cyclization and bound proteins require the consideration of DNA self-contact, a topic of contemporary interest in elasticity theory. The stability of configurations in the presence of such self-contact is a major mathematical focus of the investigator's work. On the protein side, the rod model is applied to alpha-helical protein regions that are interwound into coiled coils. The application of this model to classical polymer physics experiments, such as atomic force microscopy and single-molecule pulling experiments, should shed light on the mechanical properties of these coiled coils, in much the same way as this combination has done for DNA. The past several decades have seen the mathematical theory of elastic rods contribute considerably to the understanding of DNA. Enhancements in both the model and DNA experiments have allowed researchers to address more and more biologically interesting questions, such as the connection between base-pair sequence and DNA structure. The investigator has contributed to this research field, via several recent projects involving undergraduate research students on such questions as the flexibility of the TATA box sequence in DNA (which plays an important role in the transcribing of the genetic code to RNA) and the stability of rods in contact with obstacles (an important precursor to understanding the stability of DNA supercoiled around itself). In addition to further pursuing these studies, the investigator extends these techniques to an area where they have seen little application: proteins. There has been a growth in recent interest in coiled coils, a subset of proteins with basic structure plausibly like DNA. The investigator is in an active collaboration with a group of protein biologists, chemists, and physicists on a nanotechnology project to design protein wires using coiled coils. The expertise developed from this collaboration, combined with the investigator's experience in modeling DNA, provides an excellent opportunity to make a first step at designing a rod theory for coiled coils, which will be a useful theoretical tool in the engineering of protein wires, in much the same way that the rod model has proven useful for understanding DNA.