Theoretical Studies of the Dynamics of Proteins and their Hydration Water

Tobias MCB 0078278本项目的目标是使用分子动力学（MD）模拟，在飞秒到纳秒的时间尺度上研究天然和部分未折叠蛋白质及其溶剂的动力学。 溶剂动力学的作用，在影响蛋白质的结构松弛伴随着动态的“玻璃化”转变将使用分子MD模拟核糖核酸酶A在晶体，干燥和水合粉末，和甘油/水溶液，在温度以上和以下的过渡。 分子动力学模拟，结合中子散射实验，将被用来表征熔化球状态的α-乳白蛋白的皮秒动力学。 在模拟的本地和熔融球状态的α-乳白蛋白的表面相关的水的动力学将进行比较，试图调和的传统观点的扩大，溶剂渗透熔融球与最近报道的磁弛豫分散数据，挑战这张照片。 最后，血红素蛋白的振动能量储存和弛豫将被研究。 一系列的MD模拟将进行调查血红素冷却和耗散的振动能量的蛋白质基质和溶剂中的肌红蛋白溶液在室温下，在玻色子峰振动的能量存储血红素激发后，在低水合，低温玻璃态的肌红蛋白，和CO解离在肌红蛋白晶体中，以解决有关的问题，在时间分辨的晶体学研究中的环境影响。 非平稳时间序列分析技术将被用来产生联合的时间-频率分布，用于可视化平衡态下模式之间的振动能量流动和扰动后的振动能量弛豫。完整理解蛋白质的折叠和功能需要天然和变性蛋白质的结构，能量学和动力学知识。 该项目将提供蛋白质动力学变化的准确图像，从低温下的非活性玻璃态过渡到高温下的活性状态，以及进一步了解溶剂在影响这种转变中的作用。 此外，血红素蛋白的工作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模拟的分析提供新的工具。预计这项研究应证明是有用的蛋白质动力学的实验测量的解释，作为一个密切的对应关系与光谱实验强调在模拟的设计和结果的分析。

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.