Molecular dynamics simulations of small peptides: can one derive conformational preferences from ROESY spectra?
Molecular dynamics simulations of small peptides: can one derive conformational preferences from ROESY spectra?
复制标题
小肽的分子动力学模拟：可以从 ROESY 光谱中推导出构象偏好吗？
作者：
C. Peter;M. Rueping;H. Wörner;B. Jaun;D. Seebach;W. V. van Gunsteren
通过核磁共振实验和分子动力学模拟研究了β-二肽的折叠特性，并以此为小实验系统研究了立体中心和侧链对氢键的影响，进而对二级结构形成的影响. Val-Phe二肽和相应的Ala-Ala二肽以及Gly-Gly二肽的两种立体异构体SR和SS在甲醇中模拟40 ns。Val-Phe二肽的异构体在298 K时采用了完全不同的构象，在340 K时差异减小。有趣的是，SR异构体在较高温度下显示增强的氢键。所采用的构象主要取决于R或S侧链取代，而较少取决于侧链的类型。反算（1）H ROESY光谱和（3）J耦合常数从MD模拟和与实验数据的Val-Phe二肽的比较显示模拟和实验之间的良好的一致性，并揭示了可能的问题和陷阱，推导出一个小的和非常灵活的分子的结构特性时，从NMR数据。包括内部动力学的各个方面是必不可少的正确预测这些小分子的NMR光谱。交叉比较两种异构体的计算光谱和实验光谱表明，在许多ROESY峰中只有少数峰反映了异构体之间在298 K时相当大的构象差异。
Folding properties of beta-peptides were investigated by means of NMR experiments and MD simulations of beta-dipeptides, which serve as small test systems to study the influence of stereocenters and side chains on hydrogen-bond and consequently on secondary-structure formation. Two stereoisomers, SR and SS, of a Val-Phe dipeptide, and of the corresponding Ala-Ala dipeptide, and a Gly-Gly dipeptide were simulated in methanol for 40 ns. In agreement with experiment, the isomers of the Val-Phe dipeptide adopt quite different conformers at 298 K, the differences being reduced at 340 K. Interestingly, the SR isomer shows enhanced hydrogen bonding at the higher temperature. The adopted conformations are primarily determined by the R or S side chain substitution, and less by the type of side chain. Back-calculation of (1)H ROESY spectra and (3)J coupling constants from the MD simulations and comparison with the experimental data for the Val-Phe dipeptides shows good agreement between simulation and experiment, and reveals possible problems and pitfalls, when deriving structural properties of a small and extremely flexible molecule from NMR data only. Inclusion of all aspects of internal dynamics is essential to the correct prediction of the NMR spectra of these small molecules. Cross comparison of calculated with experimental spectra for both isomers shows that only a few out of many ROESY peaks reflect the sizeable conformational differences between the isomers at 298 K.