Intra- and intermolecular interaction inducing pyramidalization on both sides of a proline dipeptide during isomerization: an ab initio QM/MM molecular dynamics simulation study in explicit water.
Intra- and intermolecular interaction inducing pyramidalization on both sides of a proline dipeptide during isomerization: an ab initio QM/MM molecular dynamics simulation study in explicit water.
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异构化过程中分子内和分子间相互作用诱导脯氨酸二肽两侧金字塔化：在显式水中从头开始 QM/MM 分子动力学模拟研究。
DOI：
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发表时间：
2009
影响因子：
15
通讯作者：
Haruki Nakamura
中科院分区：
文献类型：
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作者：
Y. Yonezawa;K. Nakata;Kota Sakakura;T. Takada;Haruki Nakamura
脯氨酸之前肽键的顺反异构化在蛋白质折叠和生物学功能中起着重要作用。虽然已经进行了大量的实验和理论研究，但其机理尚未得到明确的阐明。利用从头算量子力学和经验分子力学的联合势，通过分子动力学模拟研究了脯氨酸二肽（Ace-Pro-NMe）在显式水中的顺反异构化过程。采用伞形采样法，得到了异构化过程中的自由能分布图。自由能格局与以往的实验值和理论值非常吻合。我们观察到，在异构化过程中，丙基氮在两个极化方向上瞬间呈锥体构象，同时丙基C-N键延伸。我们发现这些几何变化共同将脯氨基氮从sp(2)杂化电子态转变为sp(3)杂化电子态，从而实现了一个过渡态，减少了顺式和反式电子态之间的旋转障碍。我们还发现脯氨氮的水合作用稳定了负锥体构象，而分子内相互作用主要稳定了正锥体构象。在异构化过程中，锥体构象的极性和大小的波动被解释为在吡啶环的不同侧之间的氢键伙伴之间对脯氨氮的竞争。
The cis-trans isomerization of the peptide bond preceding a proline plays important roles in protein folding and biological function. Although many experimental and theoretical studies have been done, the mechanism has not yet been clearly elucidated. We studied the cis-trans isomerization of the proline dipeptide (Ace-Pro-NMe) in explicit water by molecular dynamics simulations using a combined potential derived from ab initio quantum mechanics and empirical molecular mechanics. We obtained the free energy landscape during the isomerization by using the umbrella sampling method. The free energy landscape is in good accordance with previous experimental and theoretical values. We observed that in the middle of the isomerization, the prolyl nitrogen transiently takes pyramidal conformations in two polarized directions and that, simultaneously, the prolyl C-N bond extends. We show that these geometrical changes cooperatively transform the prolyl nitrogen from a sp(2)-hybridized electronic state into a sp(3)-hybridized one, and thus realize a transition state that reduces the rotational barriers separating the cis- and trans-states. We also found that the hydration of the prolyl nitrogen stabilizes the negative pyramidal conformation, while an intramolecular interaction mainly stabilizes the positive one. Fluctuations in the polarity and magnitude of the pyramidal conformation during the isomerization are interpreted as a competition between the hydrogen-bonding partners for the prolyl nitrogen between different sides of the pyrrolidine ring.
影响因子：
2.9
作者：
Wedemeyer, WJ;Welker, E;Scheraga, HA
通讯作者：
Scheraga, HA