Li Lunna, Belcher Angela M, Loke Desmond K
Department of Biological Engineering, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.
Nanoscale. 2020 Dec 21;12(47):24214-24227. doi: 10.1039/d0nr07320b. Epub 2020 Dec 8.
The biological template and its mutants have vital significance in next generation remediation, electrochemical, photovoltaic, catalytic, sensing and digital memory devices. However, a microscopic model describing the biotemplating process is generally lacking on account of modelling complexity, which has prevented widespread commercial use of biotemplates. Here, we demonstrate M13-biotemplating kinetics in atomic resolution by leveraging large-scale molecular dynamics (MD) simulations. The model reveals the assembly of gold nanoparticles on two experimentally-based M13 phage types using full M13-capsid structural models and with polarizable gold nanoparticles in explicit solvent. Both mechanistic and structural insights into the selective binding affinity of the M13 phage to gold nanoparticles are obtained based on a previously unconsidered clamp-based binding-pocket-favored N-terminal-domain assembly and also on surface-peptide flexibility. These results provide a deeper level of understanding of protein sequence-based affinity and open the route for genetically engineering a wide range of 3D electrodes for high-density low-cost device integration.
生物模板及其突变体在下一代修复、电化学、光伏、催化、传感和数字存储设备中具有至关重要的意义。然而，由于建模复杂性，描述生物模板化过程的微观模型普遍缺乏，这阻碍了生物模板的广泛商业应用。在此，我们通过利用大规模分子动力学（MD）模拟，以原子分辨率展示了M13生物模板化动力学。该模型使用完整的M13衣壳结构模型，并在明确的溶剂中使用可极化的金纳米颗粒，揭示了金纳米颗粒在两种基于实验的M13噬菌体类型上的组装。基于先前未考虑的基于夹子的结合口袋偏好的N末端结构域组装以及表面肽的灵活性，获得了关于M13噬菌体与金纳米颗粒选择性结合亲和力的机制和结构见解。这些结果提供了对基于蛋白质序列亲和力的更深入理解，并为基因工程设计用于高密度低成本设备集成的各种3D电极开辟了道路。
