Laboratoire de Spectrométrie Ionique et Moléculaire (LASIM), Université Claude Bernard Lyon 1, 43 Bd du 11 Novembre 1918, F69622 Villeurbanne Cedex, France.
J Phys Chem A. 2008 May 22;112(20):4679-87. doi: 10.1021/jp711751f.
A multistate molecular mechanics method is introduced to model the possible competition between various protonation sites in gas-phase biomolecules with excess protons. The method relies on the Amber force field for each site and is calibrated against density-functional theory benchmark calculations at the 6-31+G(d,p) level. In its adiabatic version, where it has similarities with constant-pH algorithms, the model predicts that the small protonated Ala(4)-Lys peptide, unprotected at the N-terminus, changes protonation site above 400 K. In the larger Ala(9)-Lys+H peptide, the proton remains at the lysine amine group in a favored charge/electric dipole conformation. In the three-state Ala(4)-Lys-Ala(4)-Lys peptide, the excess proton is found to be partially delocalized on the amine group of the first lysine and on the N-terminus. The statistical properties of the protonated peptides are found to significantly depend on the localized character of the proton. Finally, the model is extended by considering possible couplings between the protonation sites, in an empirical valence-bond version. Strong couplings can stabilize the peptides into unexpected proton-bound conformations over broad ranges of temperature.
介绍了一种多态分子力学方法，用于模拟气相生物分子中过量质子与各种质子化位点之间可能存在的竞争。该方法依赖于每个位点的 Amber 力场，并通过与 6-31+G(d,p) 水平的密度泛函理论基准计算进行校准。在其绝热版本中，它与恒 pH 算法相似，模型预测在 400 K 以上时，未在 N 端保护的小质子化 Ala(4)-Lys 肽会改变质子化位点。在较大的[Ala(9)-Lys+H] (+)肽中，质子保持在赖氨酸胺基上，处于有利的电荷/电偶极构象。在三态 Ala(4)-Lys-Ala(4)-Lys 肽中，多余的质子被发现部分定域在第一个赖氨酸的胺基和 N 端上。发现质子化肽的统计性质显著取决于质子的局域性质。最后，通过考虑质子化位点之间可能存在的耦合，在经验价键版本中扩展了该模型。强耦合可以在较宽的温度范围内将肽稳定在出乎意料的质子结合构象中。
