Structural and dynamical analysis of the hydration of the Alzheimer's beta-amyloid peptide.
Structural and dynamical analysis of the hydration of the Alzheimer's beta-amyloid peptide.
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阿尔茨海默病β-淀粉样肽水合的结构和动力学分析。
DOI：
10.1002/jcc.10101
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Straub,JohnE
中科院分区：
文献类型：
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作者：
Massi,Francesca;Straub,JohnE
对淀粉样蛋白β（10 - 35）NH 2肽和淀粉样蛋白β（10 - 35）NH 2 E22 Q“Dutch”突变肽的分子动力学模拟中获得的第一溶剂化壳层中的水分子进行了分析。水化壳层中水的结构、能量学和动力学已经使用各种措施进行了研究，包括氢键网络、所有肽残基的水停留时间、扩散常数、实验确定的HN酰胺质子交换以及水从一个残基移动到另一个残基或进入本体的过渡概率。研究结果表明：（1）肽-溶剂界面处的水分子以与两种肽系统相似但与本体不同的有序结构组织，（2）肽结构相对于平行于肽表面的扩散抑制垂直于肽表面的扩散3至5倍，这与本体水的扩散相当，（3）第一溶剂化层中的水在快（1-2 ps）和慢（100 ps）时都表现出动力学弛豫。（10-40 ps）时间尺度，（4）一个新的溶剂弛豫主方程显示捕捉的肽的第一溶剂化壳水的快速弛豫的细节，（5）野生型中肽和溶剂之间的相互作用比E22 Q突变肽中的强，这与从计算机模拟获得的早期结果一致[Massi，F.;斯特劳布，J.E. Biophys J 2001，81，697]与观察到的E22 Q突变肽的增强活性相关。© 2002 Wiley Periodicals，Inc. J Comput Chem 24：143-153，2003
An analysis of the water molecules in the first solvation shell obtained from the molecular dynamics simulation of the amyloid β(10‐35)NH2peptide and the amyloid β(10‐35)NH2E22Q “Dutch” mutant peptide is presented. The structure, energetics, and dynamics of water in the hydration shell have been investigated using a variety of measures, including the hydrogen bond network, the water residence times for all the peptide residues, the diffusion constant, experimentally determined HN amide proton exchange, and the transition probabilities for water to move from one residue to another or into the bulk. The results of the study indicate that: (1) the water molecules at the peptide‐solvent interface are organized in an ordered structure similar for the two peptide systems but different from that of the bulk, (2) the peptide structure inhibits diffusion perpendicular to the peptide surface by a factor of 3 to 5 relative to diffusion parallel to the peptide surface, which is comparable to diffusion of bulk water, (3) water in the first solvation shell shows dynamical relaxation on fast (1–2 ps) and slow (10–40 ps) time scales, (4) a novel solvent relaxation master equation is shown to capture the details of the fast relaxation of water in the peptide's first solvation shell, (5) the interaction between the peptide and the solvent is stronger in the wild type than in the E22Q mutant peptide, in agreement with earlier results obtained from computer simulations [Massi, F.; Straub, J. E. Biophys J 2001, 81, 697] correlated with the observed enhanced activity of the E22Q mutant peptide. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 143–153, 2003