Effect of Ionic Aqueous Environments on the Structure and Dynamics of the A尾21鈥?0 Fragment: A Molecular-Dynamics Study

详细信息    查看全文

• 作者：Micholas Dean Smith ; Luis Cruz
• 刊名：The Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：June 6, 2013
• 年：2013
• 卷：117
• 期：22
• 页码：6614-6624
• 全文大小：407K
• 年卷期：v.117,no.22(June 6, 2013)
• ISSN：1520-5207

文摘

The amyloid 尾-protein (A尾) has been implicated in the pathogenesis of Alzheimer鈥檚 disease. The role of the structure and dynamics of the central A尾b>21鈥?0b> decapeptide region of the full-length A尾 is considered crucial in the aggregation pathway of A尾. Here we report results of isobaric鈥搃sothermal (NPT) all-atom explicit water molecular dynamics simulations of the monomeric form of the wild-type A尾b>21鈥?0b> fragment in aqueous salt environments formed by neurobiologically important group IA (NaCl, KCl) and group IIA (CaClb>2b>, MgClb>2b>) salts. Our simulations reveal the existence of salt-specific changes to secondary structure propensities, lifetimes, hydrogen bonding, salt-bridge formation, and decapeptide鈥搃on contacts of this decapeptide. These results suggest that aqueous environments with the CaClb>2b> salt, and to a much lesser extent the MgClb>2b> salt, have profound effects by increasing random coil structure propensities and lifetimes and diminishing intrapeptide hydrogen bonding. These effects are rationalized in terms of direct cation鈥揹ecapeptide contacts and changes to the hydration-shell water molecules. On the other side of the spectrum, environments with the NaCl and KCl salts have little influence on the decapeptide鈥檚 secondary structure despite increasing hydrogen bonding, salt-bridge formation, and lifetime of turn structures. The observed enhancement of open structures by group IIA may be of importance in the folding and aggregation pathway of the full-length A尾.