Theoretical Studies of the Dynamics of Proteins and their Hydration Water

本项目的目的是利用分子动力学（MD）模拟，在飞秒到纳秒的时间尺度上研究天然蛋白质和部分未折叠蛋白质及其溶剂的动力学。溶剂动力学对伴随动态“玻璃化”转变的蛋白质结构松弛的影响将通过核糖核酸酶A在晶体、干燥和水合粉末以及甘油/水溶液中的分子动力学模拟，在高于和低于转变的温度下进行研究。MD模拟，结合中子散射实验，将用于表征-乳清蛋白熔融球态的皮秒动力学。在模拟α -乳清蛋白的原生和熔融球态时，将比较表面相关水的动力学，试图将传统的膨胀、溶剂渗透熔融球的观点与最近报道的挑战这一观点的磁弛豫分散数据相调和。最后，将研究血红素蛋白的振动能量储存和弛豫。一系列的MD模拟将被用于研究血红素冷却和室温下肌红蛋白溶液中蛋白质基质和溶剂对振动能量的耗散，在低水合作用下血红素激发后玻色子峰值振动中的能量储存，肌红蛋白的低温玻璃态，以及肌红蛋白晶体中的CO解离，以解决时间分辨晶体学研究中有关环境影响的问题。非平稳时间序列分析技术将用于生成联合时频分布，以可视化振动能量在平衡态和扰动后振动能量松弛态之间的流动。要全面了解蛋白质的折叠和功能，就需要了解天然蛋白质和变性蛋白质的结构、能量学和动力学。该项目将提供蛋白质在低温下从非活性玻璃态到高温下活性态转变过程中动力学变化的准确图像，并进一步深入了解溶剂在影响这种转变中的作用。此外，对血红素蛋白的研究将有助于理解与蛋白质功能相关的基本化学动力学过程，并将为复杂蛋白质动力学的模拟分析提供新的工具。由于在模拟的设计和结果的分析中强调了与光谱实验的密切对应，预计本研究将在蛋白质动力学实验测量的解释中证明是有用的。

Tobias MCB 0078278The objective of this project is to study the dynamics of native and partially unfolded proteins and their solvent on time scales ranging from femtoseconds to nanoseconds, using molecular dynamics (MD) simulations. The role of solvent dynamics in affecting the protein structural relaxation accompanying the dynamical "glass" transition will be investigated using molecular MD simulations of ribonuclease A in crystals, dry and hydrated powders, and a glycerol/water solution, at temperatures above and below the transition. MD simulations, in conjunction with neutron scattering experiments, will be used to characterize the picosecond dynamics of the molten globule state of alpha-lactalbumin. The dynamics of surface associated water in simulations of the native and molten globule states of alpha-lactalbumin will be compared in an attempt to reconcile the traditional view of an expanded, solvent penetrated molten globule with recently reported magnetic relaxation dispersion data that challenged this picture. Finally, vibrational energy storage and relaxation in heme proteins will be investigated. A series of MD simulations will be carried out to investigate heme cooling and dissipation of vibrational energy by the protein matrix and solvent in a myoglobin solution at room temperature, the storage of energy in boson peak vibrations following heme excitation in low hydration, low temperature glassy states of myoglobin, and CO dissociation in a myoglobin crystal to address questions concerning environmental effects in time-resolved crystallographic studies. Techniques of non-stationary time series analysis will be employed to generate joint time-frequency distributions for visualizing the flow of vibrational energy between modes at equilibrium and vibrational energy relaxation following a perturbation.A complete understanding of the folding and function of proteins requires knowledge of the structures, energetics, and dynamics of native and denatured proteins. This project will provide an accurate picture of the changes in protein dynamics on making the transition from an inactive, glassy state at low temperature, to an active state at higher temperatures, as well as further insight into the role of the solvent in affecting this transition. In addition, the work on heme proteins will contribute to the understanding of fundamental chemical dynamical processes connected to protein function, and will produce new tools for the analysis of simulations of complex protein dynamics. It is anticipated that this research should prove useful in the interpretation of experimental measurements on protein dynamics, as a close correspondence with spectroscopic experiments is emphasized in the design of the simulations and the analysis of the results.