Thermodynamic and kinetic stability of the Josephin Domain closed arrangement: evidences from replica exchange molecular dynamics

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• 作者：Gianvito Grasso ; Jack A. Tuszynski ; Umberto Morbiducci ; Ginevra Licandro…
• 关键词：Ataxin ; Replica exchange molecular dynamics ; Neurodegenerative ; Josephin Domain ; Protein plasticity ; Kinetics ; Thermodynamics
• 刊名：Biology Direct
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：12
• 期：1
• 全文大小：2056KB
• 刊物主题：Life Sciences, general;
• 出版者：BioMed Central
• ISSN：1745-6150
• 卷排序：12

文摘

BackgroundMolecular phenomena driving pathological aggregation in neurodegenerative diseases are not completely understood yet. Peculiar is the case of Spinocerebellar Ataxia 3 (SCA3) where the conformational properties of the AT-3 N-terminal region, also called Josephin Domain (JD), play a key role in the first step of aggregation, having the JD an amyloidogenic propensity itself. For this reason, unraveling the intimate relationship between JD structural features and aggregation tendency may lead to a step forward in understanding the pathology and rationally design a cure. In this connection, computational modeling has demonstrated to be helpful in exploring the protein molecular dynamics and mechanism of action.