Hybrid computational–experimental data-driven design of self-assembling π-conjugated peptides
Hybrid computational–experimental data-driven design of self-assembling π-conjugated peptides
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自组装α-共轭肽的混合计算-实验数据驱动设计
DOI：
10.1039/d1dd00047k
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ferguson, Andrew L.
中科院分区：
文献类型：
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作者：
Shmilovich, Kirill;Panda, Sayak Subhra;Stouffer, Anna;Tovar, John D.;Ferguson, Andrew L.
具有电子功能的生物相容性分子为生物相容性电子器件和与生物系统的电子接口提供了有前途的基底。由侧接寡肽翼的芳香族π-核心组成的合成寡肽是一类可以在水性环境中自组装成具有涌现的光学和电子活性的超分子纳米聚集体的分子。我们提出了一个集成的计算-实验管道，在主动学习工作流程中使用全原子分子动力学模拟和实验紫外可见光谱，使用深度代表性学习和多目标和多保真度贝叶斯优化来设计π-缀合肽，该肽被编程为自组装成细长的伪1D纳米聚集体，具有π-核心的高度H型共面堆叠。我们认为作为我们的设计空间的694 982独特的π-共轭肽，其包含四噻吩π-核心，两侧是长度高达5个氨基酸的对称寡肽翼。 在通过计算仅对1181个分子（占设计空间的0.17%）进行采样和通过实验对28个分子（占设计空间的0.004%）进行采样后，我们识别并实验验证了多种先前未知的高性能分子，并提取了将肽序列与新兴超分子结构和性质联系起来的可解释的设计规则。
Biocompatible molecules with electronic functionality provide a promising substrate for biocompatible electronic devices and electronic interfacing with biological systems. Synthetic oligopeptides composed of an aromatic π-core flanked by oligopeptide wings are a class of molecules that can self-assemble in aqueous environments into supramolecular nanoaggregates with emergent optical and electronic activity. We present an integrated computational–experimental pipeline employing all-atom molecular dynamics simulations and experimental UV-visible spectroscopy within an active learning workflow using deep representational learning and multi-objective and multi-fidelity Bayesian optimization to design π-conjugated peptides programmed to self-assemble into elongated pseudo-1D nanoaggregates with a high degree of H-type co-facial stacking of the π-cores. We consider as our design space the 694 982 unique π-conjugated peptides comprising a quaterthiophene π-core flanked by symmetric oligopeptide wings up to five amino acids in length. After sampling only 1181 molecules (∼0.17% of the design space) by computation and 28 (∼0.004%) by experiment, we identify and experimentally validate a diversity of previously unknown high-performing molecules and extract interpretable design rules linking peptide sequence to emergent supramolecular structure and properties.