Megh R. Bhatt, Himal K. Ganguly and Neal J. Zondlo*,
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Moreover, the formyl group induced nearly identical α-helicity to that of the acetyl group, despite being a weaker electron donor for hydrogen bonds and for n → π* interactions. Other acyl groups exhibited intermediate α-helicity. These results indicate that the electronic properties of the acyl carbonyl do not directly determine the α-helicity in peptides in water. In order to understand these effects, DFT calculations were conducted on α-helical peptides. Using implicit solvation, α-helix stability correlated with acyl group electronics, with the pivaloyl group exhibiting closer hydrogen bonds and n → π* interactions, in contrast to the experimental results. However, DFT and MD calculations with explicit water solvation revealed that hydrogen bonding to water was impacted by the sterics of the acyl capping group. Formyl capping groups exhibited the closest water–amide hydrogen bonds, while pivaloyl groups exhibited the longest. 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引用次数: 0
摘要
相对于游离的 N 端,酰基封端基团通过提供一个额外的 C═Oi---Hi+4-N 氢键来稳定 α 螺旋。酰基封端基团的电子特性也可能直接调节α-螺旋的稳定性:富含电子的 N 端酰基基团可以通过加强 i/i + 4 氢键和 i/i + 1 n → π* 相互作用来稳定α-螺旋。这一假设在肽 X-AKAAAAKAAAAKAAGY-NH2(其中 X = 不同的酰基)中得到了验证。令人惊讶的是,电子最丰富的酰基(新戊酰基和异丁酰基)强烈地破坏了α-螺旋的稳定性。此外,尽管甲酰基在氢键和 n → π* 相互作用中是较弱的电子供体,但它诱导的 α 螺旋度几乎与乙酰基相同。其他酰基则表现出中等的α-螺旋性。这些结果表明,酰基羰基的电子特性并不能直接决定肽在水中的α-helicity。为了了解这些影响,我们对 α 螺旋肽进行了 DFT 计算。利用隐式溶解,α-螺旋稳定性与酰基电子相关,与实验结果相反,新戊酰基表现出更紧密的氢键和 n → π* 相互作用。然而,利用显式水溶解进行的 DFT 和 MD 计算表明,与水的氢键作用受到酰基封端基团立体性的影响。甲酰基封端基团表现出最接近的水-酰胺氢键,而新戊酰基则表现出最长的氢键。在 PDB 中的α-螺旋中,当 N-盖残基为 Gly 时,观察到的紧密酰胺-水氢键频率最高。实验和计算结果相结合表明,N-末端酰胺基团的溶解(水的氢键)是决定α-螺旋稳定性的核心因素。
Acyl Capping Group Identity Effects on α-Helicity: On the Importance of Amide·Water Hydrogen Bonds to α-Helix Stability
Acyl capping groups stabilize α-helices relative to free N-termini by providing one additional C═Oi···Hi+4–N hydrogen bond. The electronic properties of acyl capping groups might also directly modulate α-helix stability: electron-rich N-terminal acyl groups could stabilize the α-helix by strengthening both i/i + 4 hydrogen bonds and i/i + 1 n → π* interactions. This hypothesis was tested in peptides X–AKAAAAKAAAAKAAGY-NH2, where X = different acyl groups. Surprisingly, the most electron-rich acyl groups (pivaloyl and iso-butyryl) strongly destabilized the α-helix. Moreover, the formyl group induced nearly identical α-helicity to that of the acetyl group, despite being a weaker electron donor for hydrogen bonds and for n → π* interactions. Other acyl groups exhibited intermediate α-helicity. These results indicate that the electronic properties of the acyl carbonyl do not directly determine the α-helicity in peptides in water. In order to understand these effects, DFT calculations were conducted on α-helical peptides. Using implicit solvation, α-helix stability correlated with acyl group electronics, with the pivaloyl group exhibiting closer hydrogen bonds and n → π* interactions, in contrast to the experimental results. However, DFT and MD calculations with explicit water solvation revealed that hydrogen bonding to water was impacted by the sterics of the acyl capping group. Formyl capping groups exhibited the closest water–amide hydrogen bonds, while pivaloyl groups exhibited the longest. In α-helices in the PDB, the highest frequency of close amide–water hydrogen bonds is observed when the N-cap residue is Gly. The combination of experimental and computational results indicates that solvation (hydrogen bonding of water) to the N-terminal amide groups is a central determinant of α-helix stability.
期刊介绍:
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