Synchronous vs Asynchronous Chain Motion in α-Synuclein Contact Dynamics

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• 作者：Kristopher G. Urie ; David Angulo ; Jennifer C. Lee ; John J. Kozak ; Harry B. Gray ; Jay R. Winkler
• 刊名：Journal of Physical Chemistry B
• 出版年：2009
• 出版时间：January 15, 2009
• 年：2009
• 卷：113
• 期：2
• 页码：522-530
• 全文大小：293K
• 年卷期：v.113,no.2(January 15, 2009)
• ISSN：1520-5207

文摘

α-Synuclein (α-syn) is an intrinsically unstructured 140-residue neuronal protein of uncertain function that is implicated in the etiology of Parkinson’s disease. Tertiary contact formation rate constants in α-syn, determined from diffusion-limited electron-transfer kinetics measurements, are poorly approximated by simple random polymer theory. One source of the discrepancy between theory and experiment may be that interior-loop formation rates are not well approximated by end-to-end contact dynamics models. We have addressed this issue with Monte Carlo simulations to model asynchronous and synchronous motion of contacting sites in a random polymer. These simulations suggest that a dynamical drag effect may slow interior-loop formation rates by about a factor of 2 in comparison to end-to-end loops of comparable size. The additional deviations from random coil behavior in α-syn likely arise from clustering of hydrophobic residues in the disordered polypeptide.