Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

80-POS Board 40 Conformational Ensembles of Phase-Separating Elastin-Like Peptides from NMR and Molecular Simulations Quang Huynh 1,2 , Sean Reichheld 1 , Sarah Rauscher 2,3 , Simon Sharpe 1,2 , Régis Pomès 1,2 . 1 Hospital for Sick Children, Toronto, ON, Canada, 2 University of Toronto, Toronto, ON, Canada, 3 Max Planck Institute, Goettingen, Germany. Elastin endows skin, arteries, the lung, and the uterus with extensibility and elasticity. Elastin and elastin-like peptides are structurally disordered and self-aggregate via liquid phase separation. Despite extensive study, the structural basis for the self-assembly and the mechanical properties of elastin remains unclear. As an essential step towards elucidating the structural ensemble of elastin, we combine molecular dynamics simulations and NMR spectroscopy to study an elastin-like peptide modelled after the sequence of alternating hydrophobic and cross- linking domains of elastin. Computational and spectroscopic results are in excellent agreement. Although the peptide is highly disordered, it possesses a significant propensity for local secondary structure. The cross-linking domains are characterized by fluctuating α-helical structure, whereas the hydrophobic domains form sparse and transient hydrogen-bonded β-turns. As a result, the individual domains are collapsed but not compact, and they remain disordered and hydrated despite their predominantly hydrophobic character. These findings resolve long- standing controversies regarding the structure and function of elastin and afford insight into the physical and structural basis for the phase separation of disordered proteins.

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