Cellular crowding effects on biomolecular stability and dynamics

这项研究将把生物细胞内部的高度详细的原子论观点与它们的整体功能行为联系起来。最终的结果是一个基于基本物理原理的生物细胞模型，可以查询以全面了解各种尺度的生物过程。物理学，化学和生物化学之间以及模拟，建模和实验之间的跨学科边界的研究为培养未来几代科学家提供了独特的机会。本科生的参与是一个中心主题。来自不同学科的本科生团队将在研究生和博士后研究员的共同指导下走到一起，以强烈的跨学科视角开始第一次研究体验。妇女和代表性不足的少数群体的参与是一个主要重点。细胞环境由生物分子的密集、异质溶液组成，其中相互作用是不可避免的，但分子必须保持流体状态，并处于其天然状态，以发挥生物功能。计算机模拟与光谱实验相结合，以表征拥挤对生物分子动力学，稳定性和扩散特性的影响。沿着研究了致密蛋白质溶液以及涉及膜、染色体DNA结构和代谢物的系统。该项目的重点是表征在这种条件下发生的瞬时相互作用以及它们如何影响生物分子行为。这种洞察力将允许预测模型的建设，可以与蛋白质化学的动态和扩散行为，并最终生物功能，在体内conditions.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The research will connect the highly detailed atomistic views of the interior of biological cells with their overall functional behavior. The ultimate outcome is a model of biological cells based on basic physical principles that can be queried to gain a comprehensive understanding of biological processes across a wide range of scales. The research at interdisciplinary boundaries between physics, chemistry, and biochemistry and between simulation, modeling, and experiment provides unique opportunities for training future generations of scientists. The involvement of undergraduate students is a central theme. Teams of undergraduate students from different disciplines will come together under co-mentorship by a graduate student and postdoctoral researcher to begin first research experiences with a strong interdisciplinary perspective. The involvement of women and underrepresented minorities is a major focus.Cellular environments consist of dense, heterogeneous solutions of biomolecules where interactions are unavoidable yet molecules have to remain fluid and in their native states to carry out biological function. Computer simulations are combined with spectroscopic experiments to characterize the effects of crowding on biomolecular dynamics, stability, and diffusive properties. Dense protein solutions are studied along with systems involving membranes, chromosomal DNA structures, and metabolites. The focus of this project is on characterizing the transient interactions that occur under such conditions and how they affect biomolecular behavior. That insight will allow the construction of predictive models that can relate protein chemistry to dynamic and diffusive behavior, and ultimately biological function, under in vivo conditions.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.