Quantifying Polypeptoid Conformational Landscapes through Integrated Experiment and Simulation
Quantifying Polypeptoid Conformational Landscapes through Integrated Experiment and Simulation
复制标题
DOI：
10.1021/acs.macromol.1c00550
复制
发表时间：
2021-06
期刊：
影响因子：
5.5
通讯作者：
Sally Jiao;Audra J. DeStefano;Jacob I. Monroe;M. Barry;Nicholas Sherck;Thomas Casey;R. Segalman;Songi Han;M. Shell
中科院分区：
文献类型：
--
作者：
Sally Jiao;Audra J. DeStefano;Jacob I. Monroe;M. Barry;Nicholas Sherck;Thomas Casey;R. Segalman;Songi Han;M. Shell
我们结合实验和模拟来开发一种强大的、有效的方法来表征无序多肽的构象景观。多肽已经成为一类重要的聚合物，能够精确定义序列，同时保持革兰氏可合成的性质，推动了一系列迅速扩大的应用，包括防污剂、治疗、传感和定向自组装。多肽结构的表征提供了对序列-结构-功能关系的关键分子洞察力。结构上的无序多肽需要新的方法来研究它们在溶液中的广泛构象。在这里，我们使用双电子-电子共振(DEER)光谱和增强的采样分子建模来测量完整的端到端距离分布，而不是构型平均。我们展示了一组模型亲水性多肽的实验和模拟之间的很好的一致性。此外，我们通过表征这一多肽系列的基本聚合物物理，说明了这种实验-模拟相结合的方法在探索结构-功能关系方面的有效性，证明了这里所讨论的多肽具有排除的体积行为。
We combine experiment and simulation to develop a powerful, validated approach for characterizing the conformational landscapes of disordered polypeptoids. Polypeptoids have become an important class of polymers, capable of precisely defined sequences while remaining gram-synthesizable—properties that have driven a rapidly expanding set of applications, including antifoulants, therapeutics, sensing, and directed self-assembly. The characterization of polypeptoid structure provides critical molecular insight into sequence–structure–function relationships. Structurally disordered polypeptoids require new approaches to interrogate their wide range of conformations in solution. Here, we measure full end-to-end distance distributions, instead of configurational averages, using double electron–electron resonance (DEER) spectroscopy and enhanced sampling molecular modeling. We demonstrate excellent agreement between the experiments and simulations for a set of model hydrophilic polypeptoids. Moreover, we illustrate the utility of this combined experiment–simulation approach in probing structure–function relationships by characterizing the basic polymer physics of this polypeptoid series, demonstrating that the polypeptoids probed here exhibit excluded volume behavior.