Bergman Michael T, Xiao Xingqing, Hall Carol K
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27606, United States.
Department of Chemistry, School of Science, Hainan University, Longhua District, Haikou, Hainan 571101, China.
J Phys Chem B. 2023 Oct 5;127(39):8370-8381. doi: 10.1021/acs.jpcb.3c04319. Epub 2023 Sep 21.
Peptides that bind to inorganic materials can be used to functionalize surfaces, control crystallization, or assist in interfacial self-assembly. In the past, inorganic-binding peptides have been found predominantly through peptide library screening. While this method has successfully identified peptides that bind to a variety of materials, an alternative design approach that can intelligently search for peptides and provide physical insight for peptide affinity would be desirable. In this work, we develop a computational, physics-based approach to design inorganic-binding peptides, focusing on peptides that bind to the common plastics polyethylene, polypropylene, polystyrene, and poly(ethylene terephthalate). The PepBD algorithm, a Monte Carlo method that samples peptide sequence and conformational space, was modified to include simulated annealing, relax hydration constraints, and an ensemble of conformations to initiate design. These modifications led to the discovery of peptides with significantly better scores compared to those obtained using the original PepBD. PepBD scores were found to improve with increasing van der Waals interactions, although strengthening the intermolecular van der Waals interactions comes at the cost of introducing unfavorable electrostatic interactions. The best designs are enriched in amino acids with bulky side chains and possess hydrophobic and hydrophilic patches whose location depends on the adsorbed conformation. Future work will evaluate the top peptide designs in molecular dynamics simulations and experiment, enabling their application in microplastic pollution remediation and plastic-based biosensors.
与无机材料结合的肽可用于使表面功能化、控制结晶或协助界面自组装。过去,无机结合肽主要是通过肽库筛选发现的。虽然这种方法已成功鉴定出与多种材料结合的肽,但一种能够智能搜索肽并为肽亲和力提供物理见解的替代设计方法将是理想的。在这项工作中,我们开发了一种基于计算物理的方法来设计无机结合肽,重点关注与常见塑料聚乙烯、聚丙烯、聚苯乙烯和聚对苯二甲酸乙二酯结合的肽。PepBD算法是一种对肽序列和构象空间进行采样的蒙特卡罗方法,经过修改后纳入了模拟退火、放宽水化约束以及用于启动设计的构象集合。这些修改导致发现了与使用原始PepBD获得的肽相比得分显著更高的肽。发现PepBD得分会随着范德华相互作用的增加而提高,尽管增强分子间范德华相互作用是以引入不利的静电相互作用为代价的。最佳设计富含具有大侧链的氨基酸,并具有疏水和亲水斑块,其位置取决于吸附构象。未来的工作将在分子动力学模拟和实验中评估顶级肽设计,使其能够应用于微塑料污染修复和基于塑料的生物传感器。