The solution structure of a hexapeptide, cyclo (Gln-Trp-Phe-Gly-Leu-Met), which is a selective NK-2 antagonist, has been studied by a combination of two-dimensional nmr and molecular dynamics (MD) techniques. The simulation based on nmr and MD data resulted in the convergence to a family of structures. Free molecular dynamics for 50 ps in the presence of DMSO solvent molecules shows that the structure is energetically stable. One intramolecular hydrogen bond between the amide proton of Gln and the carbonyl oxygen of Gly was revealed. This result is consistent with the results from the measurement of the temperature coefficient of the amide protons. The extent of intermolecular hydrogen bonding between the amide protons of the peptide and DMSO was also revealed by the free MD simulation. The resulting structure of the cyclic peptide contains a variation type I' beta-turn in the Gly-Leu-Met-Gln segment. Comparison of the structure of this peptide with that of other NK-2 antagonist cyclic hexapeptides was made, and the activity of cyclic antagonists appears to be inversely related to the conformational rigidity of the cyclic peptides.

中文翻译：

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环状神经激肽拮抗剂的溶液构象：NMR和分子动力学研究。

六肽环（Gln-Trp-Phe-Gly-Leu-Met）的溶液结构是一种选择性的NK-2拮抗剂，已通过二维nmr和分子动力学（MD）技术的结合进行了研究。基于nmr和MD数据的仿真导致收敛到一系列结构。在DMSO溶剂分子存在下50 ps的自由分子动力学表明，该结构在能量上是稳定的。揭示了Gln的酰胺质子与Gly的羰基氧之间的一个分子内氢键。该结果与酰胺质子的温度系数的测量结果一致。游离的MD模拟也揭示了肽的酰胺质子和DMSO之间的分子间氢键的程度。所得环肽的结构在Gly-Leu-Met-Gln节段中包含变异型I'β-转角。对该肽的结构与其他NK-2拮抗剂环状六肽的结构进行了比较，并且环状拮抗剂的活性似乎与环状肽的构象刚性成反比。