Center for Genomics and Systems Biology, New York University, New York, New York 10003, USA.
J Am Chem Soc. 2009 Nov 25;131(46):16798-807. doi: 10.1021/ja905267k.
We present an analysis of the conformational preferences of N-substituted glycine peptoid oligomers. We survey the backbone conformations observed in experimentally determined peptoid structures and provide a comparison with high-level quantum mechanics calculations of short peptoid oligomers. The dominant sources of structural variation derive from: side-chain dependent cis/trans isomerization of backbone amide bonds, side chain stereochemistry, and flexibility in the psi dihedral angle. We find good agreement between the clustering of experimentally determined peptoid torsion angles and local torsional minima predicted by theory for a disarcosine model. The calculations describe a well-defined conformational map featuring distinct energy minima. The general features of the peptoid backbone conformational landscape are consistent across a range of N-alkyl glycine side chains. Alteration of side chain types, however, creates subtle but potentially significant variations in local folding propensities. We identify a limited number of low energy local conformations, which may be preferentially favored by incorporation of particular monomer units. Greater variation in backbone dihedral angles are accessible in peptoids featuring trans amide bond geometries. These results confirm that computational approaches can play a valuable role in guiding the design of complex peptoid architectures and may lead to strategies for introducing constraints that select among a limited number of low energy local conformations.
我们对 N-取代甘氨酸肽类低聚物的构象偏好进行了分析。我们调查了实验测定的肽类结构中观察到的骨架构象，并与短肽类低聚物的高级量子力学计算进行了比较。结构变异的主要来源来自：骨架酰胺键的侧链依赖性顺/反式异构化、侧链立体化学和 ψ 二面角的灵活性。我们发现，实验测定的肽类扭转角的聚类与理论预测的二氢神经氨酸模型的局部扭转极小值之间存在很好的一致性。计算描述了一个具有明显能量极小值的明确构象图谱。肽类骨架构象景观的一般特征在一系列 N-烷基甘氨酸侧链中是一致的。然而，侧链类型的改变会导致局部折叠倾向的微妙但潜在显著的变化。我们确定了少数几个低能量的局部构象，这些构象可能优先被特定单体单元的掺入所偏好。具有反式酰胺键几何形状的肽类可以获得更大的骨架二面角变化。这些结果证实，计算方法可以在指导复杂肽类结构的设计方面发挥有价值的作用，并可能导致引入约束的策略，从而在有限数量的低能量局部构象中进行选择。
