Peptides’ hierarchical coassembly into nanostructures enables controllable fabrication of multicomponent biomaterials. In this work, we describe a computational and experimental approach to design pairs of charge-complementary peptides that selectively coassemble into β-sheet nanofibers when mixed together but remain unassembled when isolated separately. The key advance is a peptide coassembly design (PepCAD) algorithm that searches for pairs of coassembling peptides. Six peptide pairs are identified from a pool of ~10⁶ candidates via the PepCAD algorithm and then subjected to DMD/PRIME20 simulations to examine their co-/self-association kinetics. The five pairs that spontaneously aggregate in kinetic simulations selectively coassemble in biophysical experiments, with four forming β-sheet nanofibers and one forming a stable nonfibrillar aggregate. Solid-state NMR, which is applied to characterize the coassembling pairs, suggests that the in silico peptides exhibit a higher degree of structural order than the previously reported CATCH(+/−) peptides.

中文翻译：

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从头设计共组装成基于 β 折叠的纳米原纤维的肽

肽在纳米结构中的分层组装使多组分生物材料的可控制造成为可能。在这项工作中，我们描述了一种计算和实验方法来设计成对的电荷互补肽，这些肽在混合在一起时选择性地共同组装成 β-折叠纳米纤维，但在单独分离时保持未组装。关键进展是一种肽共组装设计 (PepCAD) 算法，该算法可搜索成对的共组装肽。^{从 ~10 6}的池中鉴定出六对肽候选人通过 PepCAD 算法，然后进行 DMD/PRIME20 模拟以检查他们的共/自缔合动力学。在动力学模拟中自发聚​​集的五对在生物物理实验中选择性地共同组装，四对形成 β-折叠纳米纤维，一个形成稳定的非原纤维聚集体。用于表征共组装对的固态核磁共振表明，计算机模拟肽比之前报道的 CATCH(+/-) 肽表现出更高程度的结构有序性。