Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California, 94720.
J Comput Chem. 2014 Feb 15;35(5):360-70. doi: 10.1002/jcc.23478. Epub 2013 Nov 29.
Peptoids are positional isomers of peptides: peptoid sidechains are attached to backbone nitrogens rather than α-carbons. Peptoids constitute a class of sequence-specific polymers resistant to biological degradation and potentially as diverse, structurally and functionally, as proteins. While molecular simulation of proteins is commonplace, relatively few tools are available for peptoid simulation. Here, we present a first-generation atomistic forcefield for peptoids. Our forcefield is based on the peptide forcefield CHARMM22, with key parameters tuned to match both experimental data and quantum mechanical calculations for two model peptoids (dimethylacetamide and a sarcosine dipeptoid). We used this forcefield to demonstrate that solvation of a dipeptoid substantially modifies the conformations it can access. We also simulated a crystal structure of a peptoid homotrimer, H-(N-2-phenylethyl glycine)3 -OH, and we show that experimentally observed structural and dynamical features of the crystal are accurately described by our forcefield. The forcefield presented here provides a starting point for future development of peptoid-specific simulation methods within CHARMM.
肽缩氨酸侧链连接到主链氮原子而不是α-碳原子。肽缩氨酸构成一类序列特异性聚合物，它们能够抵抗生物降解，并且在结构和功能上可能与蛋白质一样多样化。虽然蛋白质的分子模拟已经很常见，但用于肽缩氨酸模拟的工具相对较少。在这里，我们提出了第一代肽缩氨酸原子力场。我们的力场基于肽力场 CHARMM22，关键参数经过调整，以匹配两种模型肽缩氨酸（二甲基乙酰胺和肌氨酸二肽缩氨酸）的实验数据和量子力学计算。我们使用这个力场来证明二肽缩氨酸的溶剂化作用会极大地改变它能够达到的构象。我们还模拟了一个肽缩氨酸三聚体 H-(N-2-苯乙基甘氨酸)3-OH 的晶体结构，我们表明实验观察到的晶体的结构和动力学特征都被我们的力场准确地描述了。这里提出的力场为 CHARMM 中肽缩氨酸特异性模拟方法的进一步发展提供了起点。
