Structure and dynamics of the homologous series of alanine peptides: A joint molecular dynamics/NMR study
Structure and dynamics of the homologous series of alanine peptides: A joint molecular dynamics/NMR study
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DOI：
10.1021/ja0660406
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发表时间：
2007-02-07
影响因子：
15
通讯作者：
Schwalbe, Harald
中科院分区：
文献类型：
--
作者：
Graf, Juergen;Nguyen, Phuong H.;Schwalbe, Harald
采用分子动力学（MD）模拟和核磁共振相结合的方法研究了小分子均聚模型肽的主角分布。结合测量的标量耦合常数的准确性和具有显式溶剂的全原子MD模拟的原子细节，确定了肽构象态的热居族，不确定度< 5%。三丙氨酸样品主要（类似90%）为聚l -脯氨酸II型螺旋结构，部分（类似10%）为β延伸结构，但没有α (R)螺旋构象。随着链长的增加，构象的分布没有明显变化(Ala（3)到Ala(7)）。三缬氨酸对这三种主要构象都有明显的影响。Tryglycine在Ramachandran空间的四个角区采样，并在肽键的顺式和反式构象之间存在缓慢的构象平衡。我们还研究了蛋白蛋清溶菌酶序列中在N端和c端被3个或8个氨基酸包围的片段Ala(3)的主链角分布。虽然9mer中中心三个丙氨酸残基的构象分布与小肽Ala(3)-Ala(7)相似，但在19mer中发现了主要差异，其中明显（30-40%）采用α (R)螺旋结构。
The phi,psi backbone angle distribution of small homopolymeric model peptides is investigated by a joint molecular dynamics (MD) simulation and heteronuclear NMR study. Combining the accuracy of the measured scalar coupling constants and the atomistic detail of the all-atom MD simulations with explicit solvent, the thermal populations of the peptide conformational states are determined with an uncertainty of < 5 %. Trialanine samples mainly (similar to 90%) a poly-L-proline II helix-like structure, some (similar to 10%) beta extended structure, but no alpha(R) helical conformations. No significant change in the distribution of conformers is observed with increasing chain length (Ala(3) to Ala(7)). Trivaline samples all three major conformations significantly. Tryglycine samples the four corner regions of the Ramachandran space and exists in a slow conformational equilibrium between the cis and trans conformation of peptide bonds. The backbone angle distribution was also studied for the segment Ala(3) surrounded by either three or eight amino acids on both N- and C-termini from a sequence derived from the protein hen egg white lysozyme. While the conformational distribution of the central three alanine residues in the 9mer is similar to that for the small peptides Ala(3)-Ala(7,) major differences are found for the 19mer, which significantly (30-40%) samples alpha(R) helical stuctures.