Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy.
Institute of Nanoscience, CNR-NANO S3, Via G. Campi 213/A, 41125 Modena, Italy.
Int J Mol Sci. 2022 Jan 27;23(3):1484. doi: 10.3390/ijms23031484.
Nanoscale biosensors, a highly promising technique in clinical analysis, can provide sensitive yet label-free detection of biomolecules. The spatial and chemical specificity of the surface coverage, the proper immobilization of the bioreceptor as well as the underlying interfacial phenomena are crucial elements for optimizing the performance of a biosensor. Due to experimental limitations at the microscopic level, integrated cross-disciplinary approaches that combine in silico design with experimental measurements have the potential to present a powerful new paradigm that tackles the issue of developing novel biosensors. In some cases, computational studies can be seen as alternative approaches to assess the microscopic working mechanisms of biosensors. Nonetheless, the complex architecture of a biosensor, associated with the collective contribution from "substrate-receptor-analyte" conjugate in a solvent, often requires extensive atomistic simulations and systems of prohibitive size which need to be addressed. In silico studies of functionalized surfaces also require ad hoc force field parameterization, as existing force fields for biomolecules are usually unable to correctly describe the biomolecule/surface interface. Thus, the computational studies in this field are limited to date. In this review, we aim to introduce fundamental principles that govern the absorption of biomolecules onto functionalized nanomaterials and to report state-of-the-art computational strategies to rationally design nanoscale biosensors. A detailed account of available in silico strategies used to drive and/or optimize the synthesis of functionalized nanomaterials for biosensing will be presented. The insights will not only stimulate the field to rationally design functionalized nanomaterials with improved biosensing performance but also foster research on the required functionalization to improve biomolecule-surface complex formation as a whole.
纳米级生物传感器是临床分析中极具前景的技术，可以提供对生物分子的灵敏且无需标记的检测。表面覆盖率的空间和化学特异性、生物受体的适当固定以及底层界面现象是优化生物传感器性能的关键要素。由于微观层面的实验限制，将计算设计与实验测量相结合的集成跨学科方法有可能呈现出一种强大的新范例，用于解决开发新型生物传感器的问题。在某些情况下，计算研究可以被视为评估生物传感器微观工作机制的替代方法。尽管如此，生物传感器的复杂结构，以及“基底-受体-分析物”共轭在溶剂中的集体贡献，通常需要广泛的原子模拟和庞大的系统，这需要加以解决。功能化表面的计算研究还需要特定的力场参数化，因为现有的生物分子力场通常无法正确描述生物分子/表面界面。因此，迄今为止，该领域的计算研究受到限制。在这篇综述中，我们旨在介绍控制生物分子在功能化纳米材料上吸收的基本原理，并报告用于合理设计纳米级生物传感器的最新计算策略。将详细介绍用于驱动和/或优化用于生物传感的功能化纳米材料合成的可用计算策略。这些见解不仅将激发人们合理设计具有改进的生物传感性能的功能化纳米材料，而且还将促进对整体改善生物分子-表面复合形成所需的功能化的研究。
