Laboratoire des Mécanismes Réactionnels, Department of Chemistry, Ecole Polytechnique, CNRS, Palaiseau, France.
J Phys Chem B. 2012 Jan 12;116(1):483-90. doi: 10.1021/jp207102v. Epub 2011 Dec 9.
An extensive molecular modeling study was carried out on the doubly protonated cyclic decapeptide Gramicidin S following several recent gas-phase experiments. Our computational strategy includes replica-exchange molecular dynamics simulations with the new generation force field AMOEBA for exploration and density functional calculations using several functionals for refinement of structures and computation of IR spectra. This procedure yields low-energy structures of which three are proposed to correspond to the three conformers detected in low-temperature IR experiments. The most stable structure has C(2) symmetry and four strong β-sheet interactions between Orn and Val residues. Furthermore, all the other peptidic N-H bonds are involved in seven-membered C(7) motifs. The computed IR spectra of the three conformers are in good agreement with the experimental ones in the 1400-2000 cm(-1) range. In the 3000-3600 cm(-1) region, the computed spectrum is also in good agreement with experiment for the main conformer, and predictions are made of structure-specific signatures for the other two conformers. The accuracy of several density functionals is discussed in detail. These results point out that efficient potential energy surface explorations coupled to appropriate density functional theory (DFT) calculations are able to reveal the structures of molecules as large and flexible as decapeptides.
对格兰氏菌素 S 双质子化环状十肽进行了广泛的分子建模研究，该研究基于最近的一些气相实验。我们的计算策略包括使用新一代 AMOEBA 力场进行复制交换分子动力学模拟，以探索结构，并使用几种功能进行密度泛函计算，以优化结构和计算红外光谱。该程序产生了低能量结构，其中三个被提出对应于在低温红外实验中检测到的三个构象。最稳定的结构具有 C(2)对称性和四个强β-折叠相互作用，在 Orn 和 Val 残基之间。此外，所有其他肽 N-H 键都参与了七个环的 C(7)图案。三个构象的计算红外光谱在 1400-2000 cm(-1) 范围内与实验结果非常吻合。在 3000-3600 cm(-1) 区域，主要构象的计算光谱与实验也非常吻合，并对其他两个构象的结构特异性特征进行了预测。详细讨论了几种密度泛函的准确性。这些结果表明，有效的势能面探索与适当的密度泛函理论（DFT）计算相结合，能够揭示像十肽这样大而灵活的分子的结构。
