Spectrin is a filamentous protein responsible for the elasticity of red blood cells. While the full spectrin tetramer has a contour length of approximately 200 nm, it is composed of a number of repeating domains, called spectrin repeat units, each about 6 nm long.This research aims to use atomistic molecular dynamics simulations of the repeat units in conjunction with coarse-grained modeling of the larger spectrin structures in order to understand both the structural and dynamical origins of this elasticity.
      Atomic force microscopy (AFM) has been an important experimental tool used to examine the force-extension behavior, and thus the elasticity, of spectrin molecules consisting of several repeat units. The experiments probe extensions that result in rupturing the repeat units and give a saw tooth-shaped force-extension curve, where the peaks are attributed to the force required to rupture a repeat unit.

     While it is not known whether rupturing of the repeat units plays any physiological role in the red blood cells, the AFM experiments do raise some important questions concerning the relationship between the structure and function of proteins. Of primary interest to our work is the fact that the forces required to rupture the repeat units in the AFM experiments (which are performed over milliseconds) is more than an order of magnitude smaller than the forces required to rupture repeat units using atomistic simulation (which are performed over nanoseconds).
      The specific goal of this work is to develop coarse-grained models of spectrins consisting of several repeat units which are parameterized from atomistic simulations. The coarse grained models can then be used to examine the rupture behavior over a large range of time-scales, and could even be used under conditions approaching those of physiological conditions and could thus help to answer the question of whether the rupture behavior plays any important physiological role.