Using Enhanced Sampling Simulations to Study the Conformational Space of Chiral Aromatic Peptoid Monomers
Using Enhanced Sampling Simulations to Study the Conformational Space of Chiral Aromatic Peptoid Monomers
复制标题
DOI：
10.1021/acs.jctc.3c00803
复制
发表时间：
2023-11-08
影响因子：
5.5
通讯作者：
Santiso，Erik E.
中科院分区：
文献类型：
--
作者：
Jain，Rakshit Kumar;Hall，Carol K.;Santiso，Erik E.
类肽或N-取代的甘氨酸是肽样物质，由于其增强的柔性和可能的侧链的多样性集合而形成各种各样的二级结构。与肽相比，类肽具有基本上更复杂的构象景观。这主要是由于类肽酰胺键同时存在于顺式和反式构象中的能力。这使得传统的分子动力学模拟，甚至一些增强的采样方法无法采样完整的能量景观。在这篇文章中，我们提出了一个扩展CGenFF-NTOID类肽原子力场添加参数的四个侧链到以前可用的集合。我们采用显式溶剂回火metadhesics模拟，以优化我们的力场参数和平行偏置metadhesics研究thecis-transomerism的SN 1-苯乙基（s1 pe）和SN 1-萘乙基（s1 ne）类肽单体，自由能最小值，从可用的实验数据进行验证。在实验数据的情况下，我们支持我们的原子模拟从头计算。这项工作代表了基于肽的材料的计算设计的重要一步。
Peptoids, or N-substituted glycines, are peptide-like materials that form a wide variety of secondary structures owing to their enhanced flexibility and a diverse collection of possible side chains. Compared to that of peptides, peptoids have a substantially more complex conformational landscape. This is mainly due to the ability of the peptoid amide bond to exist in bothcis- andtrans-conformations. This makes conventional molecular dynamics simulations and even some enhanced sampling approaches unable to sample the complete energy landscapes. In this article, we present an extension to the CGenFF-NTOID peptoid atomistic forcefield by adding parameters for four side chains to the previously available collection. We employ explicit solvent well-tempered metadynamics simulations to optimize our forcefield parameters and parallel bias metadynamics to study thecis–transisomerism for SN1-phenylethyl (s1pe) and SN1-naphthylethyl (s1ne) peptoid monomers, the free energy minima generated from which are validated with available experimental data. In the absence of experimental data, we supported our atomistic simulations withab initiocalculations. This work represents an important step toward the computational design of peptoid-based materials.