EAGER: Electrical detection of individual biomolecular interactions and machine learning-assisted simulations: from single-molecule biophysics to the RISC complex

这项EAGER奖将资助开发一种新的基于纳米技术的方法，以测量两种或多种蛋白质之间或蛋白质与核酸之间的生物分子相互作用。这些类型的相互作用是相互作用是大多数生化过程的核心。在这项工作中开发的新方法可以应用于许多生物学问题，为生物物理学的全新知识体系铺平了道路。这项研究将提高下一代生物化学家、科学家和工程师的培训和教育可能性，并通过培训他们使用现代机器学习工具来改善劳动力。该项目还将促进妇女和代表性不足的少数民族参与STEM。拟议的研究将使用新的纳米技术方法来测量与生物分子相互作用相关的电导率。该项目的总体目标是生物分子相互作用的电子量化，包括作为概念验证的热力学和动力学信息。该方法的核心假设是，来自生物分子相互作用的电子指纹包含与该复合物的生物功能相关的热力学和动力学信息。对单个生物分子之间相互作用动力学的直接观察，将使我们能够在生物分子相互作用的生物化学基础上，发展出完整的生物物理图景。该研究提供了完全不同的跨学科方法，基于实验方面的单分子生物物理学和生物化学专业知识，以及在计算方面使用分子动力学和量子化学的广泛理论驱动的计算机模拟经验。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This EAGER award will fund the development of a novel nanotechnology based method to measure biomolecular interactions between two or more proteins or between proteins and nucleic acids. These types of interactions are interactions are at the heart of most biochemical processes. The new method developed in this work could be applied to numerous biological problems, paving the way to a whole new body of knowledge in biophysics. This research will enhance the training and education possibilities of the next generations of biochemists, scientists, and engineers in general, and improve the workforce by training them to use the modern machine-learning tools. This project will also promote the STEM participation of women and underrepresented minorities.The proposed research will use novel nanotechnology methods to measure the electrical conductivities related to biomolecular interactions. The overall objective for this project is the electronic quantification of biomolecular interactions, including both thermodynamic and kinetic information as a proof-of-concept. The central hypothesis of this approach is that electronic fingerprints from biomolecular interactions contain thermodynamic and kinetic information that correlate with the biological function of this complex. The direct observation of the dynamics of interaction between individual biomolecules will allow a development of a complete biophysical picture underlying the biochemistry of biomolecular interactions. The research offers radically different interdisciplinary approach based on expertise in single-molecule biophysics and biochemistry in the experimental front, and extensive theory-driven computer simulations experience using Molecular Dynamics and Quantum Chemistry on the computational side.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.