PhD, University of Cincinnati, 2010, Arts and Sciences : Physics

Resilin is an elastomeric protein characterized by rubber-like elasticity, very high resilience and high fatigue lifetime. These outstanding material properties are conferred by multiple elastic repeats, similar to those found in other elastomeric proteins. In this thesis I use molecular dynamics to elucidate the effect of amino-acid sequence variation on the mechanical properties of resilin-like peptides. In particular, I address the role of disorder in the relaxed (unstretched) state and the amount of conformational entropy lost upon extension. I simulate model systems comprising multiple identical repeats from single elastic units observed in fruit fly and mosquito resilin gene products. The length of the simulated peptides ranges from 11 to 176 residues. In order to study the nature of the restoring force in resilin I use steered molecular dynamics (SMD) and fixed end simulations. I find a high level of disorder and lack of stable secondary structure for the well solvated relaxed state in all simulated peptides; these results are consistent with conclusions from circular dichroism spectra of resilin-like peptides. Structural parameters, computed from molecular dynamics trajectories, are compared with experimental NMR and SAXS results. While upon stretching the conformational entropy is significantly decreased, the enthalpy is estimated to remain essentially unchanged. I conclude that the restoring force is primarily of entropic origin and largely insensitive to the amino-acid composition of resilin-like elastic repeats. Finally, I build a coarse-grained model from all-atomic simulation of two repeats in mosquito resilin and apply it larger peptides in order to assess flexibility and the effect of cross-linking in multiple resilin-like polypeptides.

Committee: Thomas Beck PhD (Committee Chair); Jaroslaw Meller PhD (Committee Member); Rostislav Serota PhD (Committee Member) Subjects: Biophysics