Department of Chemistry, City University of New York-Hunter College and Graduate School, 695 Park Avenue, New York, New York 10065, United States.
J Phys Chem B. 2011 Sep 8;115(35):10560-6. doi: 10.1021/jp205388q. Epub 2011 Aug 11.
We present ONIOM calculations using B3LYP/d95(d,p) as the high and AM1 as the low level on parallel β-sheets containing from two to ten strands of Ac-VQIVYK-NHMe and Ac-VQIINK-NHMe, as well as both parallel and antiparallel Ac-AAAAAA-NHMe. We find that the first two sequences form more stable sheets due to the additional H-bonding between the Q's in the side chains of both and the N's in the side chain of Ac-VQIINK-NHMe. However, the H-bonds in the amyloid chains are significantly weakened by attractive strain, which prevents all the interstrand H-bonds from achieving their optimal geometries simultaneously and requires high distortion energies for the individual strands in the sheets. The antiparallel Ac-AAAAAA-NHMe's are generally more stable and more cooperative than the parallel sheets, principally due to the higher distortion energies of the latter.
我们使用 ONIOM 计算，B3LYP/d95(d,p) 作为高精度级别，AM1 作为低精度级别，计算了包含两条到十条链的 Ac-VQIVYK-NHMe 和 Ac-VQIINK-NHMe 平行 β-折叠片以及 Ac-AAAAAA-NHMe 的平行和反平行结构。我们发现，前两个序列形成更稳定的折叠片，是因为侧链 Q 之间以及 Ac-VQIINK-NHMe 侧链 N 之间的额外氢键作用。然而，淀粉样纤维中的氢键由于吸引力应变而显著减弱，这阻止了所有链间氢键同时达到最佳构象，并且需要折叠片中各个链的高变形能。反平行 Ac-AAAAAA-NHMe 通常比平行折叠片更稳定且更具协同性，主要是因为后者具有更高的变形能。
