Department of Materials Science and Technology , University of Crete , Heraklion 700 13 , Crete , Greece.
Institute of Electronic Structure and Laser (IESL) FORTH , Heraklion 711 10 , Crete , Greece.
J Phys Chem B. 2018 Aug 2;122(30):7555-7568. doi: 10.1021/acs.jpcb.8b04103. Epub 2018 Jul 20.
Amyloid materials are gaining increasing attention as promising materials for applications in numerous fields. Computational methods have been successfully implemented to investigate the structures of short amyloid-forming peptides, yet their application in the design of functional amyloid materials is still elusive. Here, we developed a computational protocol for the design of functional amyloid materials capable of binding to an ion of interest. We applied the protocol in a test case involving the design of amyloid materials with cesium ion deposition and capture properties. As part of the protocol, we used an optimization-based design model to introduce mutations at non-β-sheet residue positions of an amyloid designable scaffold. The designed amino acids introduced to the scaffold mimic how amino acids bind to cesium ions according to experimentally resolved structures and also aim at energetically stabilizing the bound conformation of the pockets. The optimum designs were computationally validated using a series of simulations and structural analysis to select the top designed peptides, which are predicted to form fibrils with cesium ion binding properties for experimental testing. Experiments verified the amyloid-forming properties of the selected top designed peptides, as well as the cesium ion deposition and capture properties by the amyloid materials formed. This study demonstrates the first, to the best of our knowledge, computational design protocol to functionalize amyloid materials for ion binding properties and suggests that its further advancement can lead to novel, highly promising functional amyloid materials of the future.
淀粉样物质作为在众多领域有应用前景的材料越来越受到关注。计算方法已成功应用于研究短淀粉样形成肽的结构，但将其应用于功能性淀粉样材料的设计仍然难以捉摸。在这里，我们开发了一种用于设计能够结合感兴趣离子的功能性淀粉样材料的计算方案。我们将该方案应用于一个涉及具有铯离子沉积和捕获性能的淀粉样材料设计的测试案例中。作为该方案的一部分，我们使用基于优化的设计模型在淀粉样可设计支架的非β-折叠残基位置引入突变。设计引入支架的氨基酸模拟了根据实验解析结构结合铯离子的氨基酸，并且还旨在稳定口袋的结合构象。使用一系列模拟和结构分析对最佳设计进行了计算验证，以选择具有铯离子结合性能的顶级设计肽，这些肽有望用于实验测试形成原纤维。实验验证了所选顶级设计肽的淀粉样形成特性，以及形成的淀粉样材料的铯离子沉积和捕获特性。这项研究首次展示了用于离子结合特性的功能性淀粉样材料的计算设计方案，并且表明其进一步发展可以导致未来具有高度前景的新型功能性淀粉样材料。
