van der Spoel D, van Buuren A R, Tieleman D P, Berendsen H J
Bioson Research Institute, University of Groningen, The Netherlands.
J Biomol NMR. 1996 Oct;8(3):229-38. doi: 10.1007/BF00410322.
Molecular dynamics (MD) simulations of short peptides in water were performed to establish whether it is possible to reproduce experimental data from chemical shift measurements by nuclear magnetic resonance spectroscopy. Three different tetrapeptides were studied. The first, YTGP (Tyr-Thr-Gly-Pro), shows an electrostatic interaction between the aromatic ring of Tyr and the backbone amide hydrogen atom of Gly. The second, YTAP (Tyr-Thr-Ala-Pro), cannot make such an interaction because of steric hindrance of the Ala side chain and hence does not show a well-defined conformation. The third, FTGP (Phe-Thr-Gly-Pro), is shown to alternate between two different conformations. It is demonstrated that small differences in chemical shift, corresponding to these slightly different conformations, can be quantitatively modeled in MD simulations when using the proper force-field parameters and water model Explicit inclusion of hydrogen atoms o the aromatic rings is essential for a proper description of electrostatic interactions, but the choice of the water model is equally important. We found that a combination of the SPC/E water model and a revised GROMOS87 force field gives close agreement with experiment, while the same and other force fields in combination with SPC or TIP3P water did not reproduce the NMR data at all. Simulations of a longer peptide from bovine pancreatic trypsin inhibitor, containing the YTGP sequence, did show the interaction between the aromatic ring and the amide hydrogen, but not as pronounced as the simulations of shorter periods.
对水中短肽进行了分子动力学（MD）模拟，以确定是否有可能通过核磁共振光谱法从化学位移测量中重现实验数据。研究了三种不同的四肽。第一种，YTGP（酪氨酸-苏氨酸-甘氨酸-脯氨酸），在酪氨酸的芳香环与甘氨酸的主链酰胺氢原子之间显示出静电相互作用。第二种，YTAP（酪氨酸-苏氨酸-丙氨酸-脯氨酸），由于丙氨酸侧链的空间位阻，无法形成这种相互作用，因此没有显示出明确的构象。第三种，FTGP（苯丙氨酸-苏氨酸-甘氨酸-脯氨酸），显示出在两种不同构象之间交替。结果表明，当使用适当的力场参数和水模型时，在MD模拟中可以对与这些略有不同构象相对应的化学位移的微小差异进行定量建模。明确包含芳香环上的氢原子对于正确描述静电相互作用至关重要，但水模型的选择同样重要。我们发现，SPC/E水模型和修订后的GROMOS87力场的组合与实验结果非常吻合，而相同的和其他力场与SPC或TIP3P水的组合根本无法重现NMR数据。对来自牛胰蛋白酶抑制剂的包含YTGP序列的较长肽的模拟确实显示了芳香环与酰胺氢之间的相互作用，但不如较短周期的模拟那么明显。
