Insights into a putative hinge region in elastin using molecular dynamics simulations

The resiliency and elasticity of vertebrate tissues are traced to elastin, a crosslinked protein with extensive hydrophobic regions. There is little discussion in the literature on the structure and dynamics of the alanine-rich crosslinking regions of elastin that comprise a significant part of the native protein. In particular, the region encoded by exons 21 and 23, a contiguous splice form found in all types of human elastin, is believed to be strategically positioned for proper function of the protein, namely, in the reversible elongation and contraction of tissue. Hence, molecular dynamics (MD) calculations on the EX21/23 domain are reported here. This crosslinking domain has been assumed to adopt an architecture in which the putative hinge region links two α-helices. In this paper, we use a homology-based approach to obtain starting structures in the hinge region. The subsequent MD brings new insights into the possibility of fluctuations between “open” and “closed” states, as well as distinguishing structural features of the latter. The significance of these findings towards an enhanced understanding of structure–function relationships in elastin and the elastic fiber is discussed.