Capping parallel β-sheets of acetyl(Ala)6NH2 with an acetyl(Ala)5ProNH2 can arrest the growth of the sheet, suggesting a potential for curtailing amyloid growth. An ONIOM and density functional theory study.
Capping parallel β-sheets of acetyl(Ala)6NH2 with an acetyl(Ala)5ProNH2 can arrest the growth of the sheet, suggesting a potential for curtailing amyloid growth. An ONIOM and density functional theory study.
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DOI：
10.1021/bi401366w
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发表时间：
2014-02-04
期刊：
影响因子：
2.9
通讯作者：
Dannenberg, J. J.
中科院分区：
文献类型：
--
作者：
Pohl, Gabor;Asensio, Amparo;Dannenberg, J. J.
我们使用B3 LYP/d95（d，p）作为高水平，AM 1作为中水平，对含有四股Ac-AAAAAA-NH 2的平行β折叠进行ONIOM计算，其中Ac-AAPAAA-NH 2或Ac-AAAPAA-NH 2封端。由于Pro只能从肽键的一侧（含有C=O氢键受体的一侧）形成氢键，因此两条含Pro链中只有一条可以有利地添加到每一侧的片上。令人惊讶的是，当片在一个边缘用AAPAAA-NH 2封端时，封端和片之间的相互作用比另一个全Ala链的相互作用稍微更稳定。分解成氢键和畸变能的相互作用的相互作用的能量显示出有利的相互作用是由于在链和四链片的较低的畸变能。由于另一条链将被抑制附着到另一侧的加帽（Pro-含）链，我们建议可能使用的Pro残基的肽设计，以阻止许多淀粉样蛋白的生长。
We present ONIOM calculations using B3LYP/d95(d,p) as the high level and AM1 as the medium level on parallel β-sheets containing four strands of Ac-AAAAAA-NH2 capped with either Ac-AAPAAA-NH2 or Ac-AAAPAA-NH2. Because Pro can form H-bonds from only one side of the peptide linkage (that containing the C=O H-bond acceptor), only one of the two Pro-containing strands can favorably add to the sheet on each side. Surprisingly, when the sheet is capped with AAPAAA-NH2 at one edge, the interaction between the cap and sheet is slightly more stabilizing than that of another all Ala strand. Breaking down the interaction enthalpies into H-bonding and distortion energies shows the favorable interaction to be due to lower distortion energies in both the strand and the four-stranded sheet. Because another strand would be inhibited for attachment to the other side of the capping (Pro-containing) strand, we suggest the possible use of Pro residues in peptides designed to arrest the growth of many amyloids.
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