CAREER: Ultrafast hydrogen-bond dynamics in crowded, heterogeneous environments

在化学系化学结构动力学与机理(CSDM-A)项目的资助下，德克萨斯大学奥斯汀分校的卡洛斯·贝兹教授正在研究生物分子在拥挤环境中的结构和运动。像蛋白质和DNA这样的生物分子(生物分子)可以包含许多原子(数千个！)这意味着它们的结构和内部运动(弯曲、扭曲、折叠)可能非常复杂和难以预测。为了了解生物分子，化学家们在稀溶液中研究了它们，换句话说，在它们与周围的水分子相互作用的条件下，而不是在其他大的生物分子的条件下。最近有证据表明，在稀溶液中的这些研究结果可能不能代表生物环境。在真实的活细胞中，生物分子存在于拥挤的环境中并发挥作用，通常聚集在一起形成膜、酶复合体和细胞器。生物分子在真实拥挤条件下的实际行为是什么？贝兹教授和他的学生正在使用一种名为时间分辨二维红外光谱(2D IR)的技术来研究分子在更真实、更拥挤的环境中的结构和运动。为了帮助解释复杂的2D IR数据，贝兹教授正在为拥挤的系统开发计算机模型。总之，实验和计算研究正在形成分子结构、环境和动力学之间的联系，以使细胞内蛋白质相互作用的机制合理化。通过这个项目，贝兹教授和他的学生们提供了对生命系统如何在分子水平上发挥作用的见解。这项研究还可能带来新的低温保护剂技术(低温保护剂是一种化学物质，在细胞冷冻时会阻碍有害冰晶的形成)。从事这个项目的学生在前沿激光光学技术以及分子系统的计算机模拟方面获得了宝贵的技能和经验。该项目的更广泛影响旨在通过为西南部各州代表性不足的学生组织访问日，增加德克萨斯大学奥斯汀分校化学研究生项目的少数族裔学生的代表性。这些努力旨在促进未来科技工作者的多样性。这个项目的重点是绘制在含有聚合物和蛋白质等排泄剂的溶液中模仿蛋白质主干的小分子的超快氢键动力学，以表征拥挤和限制对溶剂化动力学的影响。超快二维红外光谱被用来提取频率-频率关联函数，并将其直接与分子动力学模拟进行比较。基于结构的红外图用于从分子动力学轨迹生成光谱，从而在实验和模拟之间提供直接联系。振动探头，包括硫氰酸盐，用于进入蛋白质表面的溶剂化环境，以了解蛋白质极性和静电学对局部氢键网络的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With funding by the Chemical Structure Dynamics and Mechanism (CSDM-A) program of the Chemistry Division, Professor Carlos Baiz of the University of Texas at Austin is investigating the structure and motions of biological molecules in "crowded" environments. Biological molecules (biomolecules) like proteins and DNA can contain many atoms (thousands!). This means that their structures and internal motions (bending, twisting, folding) can be very complicated and hard to predict. In order to understand biomolecules, chemists have studied them in dilute solution, in other words, under conditions where they are interacting with surrounding water molecules, but not other large biomolecules. It has recently become evident that findings from these studies in dilute solution may not be representative of biological environments. In real living cells, biomolecules exist and function in crowded environments, often assembled together to form membranes, enzyme complexes, and organelles. What are the actual behaviors of biomolecules in real, crowded conditions? Professor Baiz and his students are using a technique called time-resolved, two-dimensional, infrared spectroscopy (2D IR) to study the structure and motions of molecules in more realistic, crowded environments. In order to help interpret the complicated 2D IR data, Professor Baiz is developing computer models for the crowded systems. Together, the experimental and computational studies are forming connections among molecular structure, environments, and dynamics to rationalize the mechanisms of protein interactions in the cell. Through this project, Professor Baiz and his students are providing insights into how living systems function at the molecular level. The research may also lead to new cryoprotectant technologies (cryoprotectants are chemical substances that hinder the formation of detrimental ice crystals in cells when they are frozen). The students engaged in this project are gaining valuable skills and experience in cutting edge laser optics technology as well as in the computer simulation of molecular systems. The broader impacts of this project aim to increase representation from minority students in the Chemistry graduate program at the University of Texas at Austin through organized visit days for underrepresented students across the southwestern states. These efforts seek to boost diversity among the future science and technology workforce.This project focuses on mapping the ultrafast hydrogen-bond dynamics of small molecules that mimic the protein backbone in solutions with crowding agents such as polymers and proteins to characterize the effects of crowding and confinement on solvation dynamics. Ultrafast two-dimensional infrared spectroscopy is used to extract frequency-frequency correlation functions, which are directly compared to molecular dynamics simulations. Structure-based infrared maps are used to generate spectra from molecular dynamics trajectories, and thus provide a direct connection between experiments and simulations. Vibrational probes, including thiocyanates, are used to access the solvation environments on the surface of proteins to understand the effect of protein polarity and electrostatics on local hydrogen-bond networks.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.