Structure and Dynamics of Elastin Cross-linking Domains

The secondary structure of elastin cross-linking domains has been shown to be sequence and context dependent, but the role of these domains in the function of elastomeric proteins remains unclear. We use molecular dynamics simulations (MD), circular dichroism spectroscopy (CD), and nuclear magnetic resonance to probe the conformational equilibria of model elastin-like cross-linking peptides. We tested four recently developed force fields using MD to select the one that best reproduces the amount of alpha-helix seen in CD. Simulation studies of the aggregative properties of the cross-linking domains found that they occasionally interact, but not in any specific way. Additionally, multifaceted studies of biphasic systems show that these domains do not partition preferentially into or on the interface of a hydrophobic surface. Further experiments on constructs of cross-linking and hydrophobic domains will help elucidate how cross-linking modulates the self-assembly and mechanical properties of elastomeric proteins.M.Sc