Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Biopolymers. 2011 Jan;95(1):51-61. doi: 10.1002/bip.21534.
Conformational preferences and prolyl cis-trans isomerizations of the (2S,4S)-4-methylproline (4S-MePro) and (2S,4R)-4-methylproline (4R-MePro) residues are explored at the M06-2X/cc-pVTZ//M06-2X/6-31+G(d) level of theory in the gas phase and in water, where solvation free energies were calculated using the implicit SMD model. In the gas phase, the down-puckered γ-turn structure with the trans prolyl peptide bond is most preferred for both Ac-4S-MePro-NHMe and Ac-4R-MePro-NHMe, in which the C(7) hydrogen bond between two terminal groups seems to play a role, as found for Ac-Pro-NHMe. Because of the C(7) hydrogen bonds weakened by the favorable direct interactions between the backbone C==O and H--N groups and water molecules, the 4S-MePro residue has a strong preference of the up-puckered polyproline II (PP(II)) structure over the down-puckered PP(II) structure in water, whereas the latter somewhat prevails over the former for the 4R-MePro residue. However, these two structures are nearly equally populated for Ac-Pro-NHMe. The calculated populations for the backbone structures of Ac-4S-MePro-NHMe and Ac-4R-MePro-NHMe in water are reasonably consistent with CD and NMR experiments. In particular, our calculated results on the puckering preference of the 4S-MePro and 4R-MePro residues with the PP(II) structures are in accord with the observed results for the stability of the (X-Y-Gly)(7) triple helix with X = 4R-MePro or Pro and Y = 4S-MePro or Pro. The calculated rotational barriers indicate that the cis-trans isomerization may in common proceed through the anticlockwise rotation for Ac-4S-MePro-NHMe, Ac-4R-MePro-NHMe, and Ac-Pro-NHMe in water. The lowest rotational barriers become higher by 0.24-1.43 kcal/mol for Ac-4S-MePro-NHMe and Ac-4R-MePro-NHMe than those for Ac-Pro-NHMe in water.
在气相中和水中，使用隐式 SMD 模型计算溶剂化自由能，在 M06-2X/cc-pVTZ//M06-2X/6-31+G(d)理论水平上探索了（2S,4S）-4-甲基脯氨酸（4S-MePro）和（2S,4R）-4-甲基脯氨酸（4R-MePro）残基的构象偏好和脯氨酸顺反异构化。在气相中，对于 Ac-4S-MePro-NHMe 和 Ac-4R-MePro-NHMe，最优先的是下卷曲的γ-转角结构，其中顺式脯氨酸肽键，两个末端基团之间的 C(7)氢键似乎起到了作用，就像 Ac-Pro-NHMe 一样。由于 C(7)氢键被骨架 C==O 和 H--N 基团与水分子之间的有利直接相互作用削弱，4S-MePro 残基在水中强烈倾向于上卷曲的多聚脯氨酸 II（PP(II)）结构，而不是下卷曲的 PP(II)结构，而对于 4R-MePro 残基，后者略占优势。然而，这两种结构对于 Ac-Pro-NHMe 几乎是等概率的。在水中，Ac-4S-MePro-NHMe 和 Ac-4R-MePro-NHMe 的骨架结构的计算出的种群与 CD 和 NMR 实验相当一致。特别是，我们对 4S-MePro 和 4R-MePro 残基与 PP(II)结构的卷曲偏好的计算结果与观察到的（X-Y-Gly）（7）三螺旋体稳定性的结果一致，其中 X = 4R-MePro 或 Pro，Y = 4S-MePro 或 Pro。计算出的旋转势垒表明，顺反异构化可能通常通过 Ac-4S-MePro-NHMe、Ac-4R-MePro-NHMe 和 Ac-Pro-NHMe 在水中的逆时针旋转进行。对于 Ac-4S-MePro-NHMe 和 Ac-4R-MePro-NHMe，在水中的最低旋转势垒比 Ac-Pro-NHMe 高 0.24-1.43 kcal/mol。
