School of Physics and Astronomy, University of Leeds, Leeds, United Kingdom, LS2 9JT.
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom LS2 9JT.
Biomacromolecules. 2023 Nov 13;24(11):4869-4879. doi: 10.1021/acs.biomac.3c00583. Epub 2023 Oct 24.
Fundamental understanding of the structure and assembly of nanoscale building blocks is crucial for the development of novel biomaterials with defined architectures and function. However, accessing self-consistent structural information across multiple length scales is challenging. This limits opportunities to exploit atomic scale interactions to achieve emergent macroscale properties. In this work we present an integrative small- and wide-angle neutron scattering approach coupled with computational modeling to reveal the multiscale structure of hierarchically self-assembled β hairpins in aqueous solution across 4 orders of magnitude in length scale from 0.1 Å to 300 nm. Our results demonstrate the power of this self-consistent cross-length scale approach and allows us to model both the large-scale self-assembly and small-scale hairpin hydration of the model β hairpin CLN025. Using this combination of techniques, we map the hydrophobic/hydrophilic character of this model self-assembled biomolecular surface with atomic resolution. These results have important implications for the multiscale investigation of aqueous peptides and proteins, for the prediction of ligand binding and molecular associations for drug design, and for understanding the self-assembly of peptides and proteins for functional biomaterials.
对纳米尺度构建块的结构和组装的基本理解对于开发具有明确结构和功能的新型生物材料至关重要。然而，获取跨越多个长度尺度的一致结构信息具有挑战性。这限制了利用原子尺度相互作用来实现宏观尺度性质的机会。在这项工作中，我们提出了一种综合的小角和广角中子散射方法，并结合计算建模，揭示了在 0.1 Å 到 300nm 的 4 个数量级的长度尺度范围内，在水溶液中分级自组装 β 发夹的多尺度结构。我们的结果证明了这种自洽的跨长度尺度方法的强大功能，并使我们能够对模型 β 发夹 CLN025 的大规模自组装和小尺度发夹水合进行建模。使用这种技术组合，我们以原子分辨率绘制了该模型自组装生物分子表面的疏水性/亲水性特征。这些结果对于水肽和蛋白质的多尺度研究、预测配体结合和药物设计中的分子相互作用以及理解功能性生物材料的肽和蛋白质自组装具有重要意义。
