微重力环境下非稳态自然对流传质对蛋白质晶体生长特性影响

The particular nature and physiological function of proteins are closely related to specific structures of protein molecules. Only after a lot of protein structures and functions has been recognized, researchers can understand the secrets of life and design drugs. The primary task of three-dimensional structure determinations of proteins is to obtain their crystals with high quality. Commonly, protein crystals are always growing from solution. On the earth, as a result of protein crystal growth, density gradients occurs and leads to natural convection under normal gravity field. Convection in solution is one of the most important factors determining growth rate and the quality of protein crystals. Microgravity environment which can reduce gravity-caused convection is considered as ideal environment for protein crystal growth. But the quality of only a few protein crystals growing under microgravity has improved obviously. In fact, due to the existence of unsteady disturbances under microgravity, convection in solution is inevitable in the process of protein crystal growth. This project intends to explore the reasons why some of protein crystals growing in microgravity have not show apparent improvement in quality. Based on a dimensionless number r of evaluating protein molecular motion characteristics, which is decided by the coupling interaction between convection and diffusivity, equipped with theoretical analysis and numerical calculation methods, this project tries to carry out the studies with the main contents as: (1) considering different disturbance factors (such as g-gitter), the different shapes of protein crystals and containers of solution, under microgravity a real unsteady model of convection in the solution which protein crystal grows in will be developed to obtain the velocity and temperature fields; (2) according to the results of velocity and temperature fields, the dimensionless number r will be calculated, the dependence of r on microgravity level can be obtained, the influence of frequencies and amplitudes of the disturbance factors on the value of r is investigated, the characteristics of r is classified under microgravity; (3) the value of r is used for evaluating the effects of unsteady natural convection on protein crystal growth and compared with the value of r on the earth, the mechanism of unsteady convection affecting on protein crystal growth is expected to be disclosed, the reasons why some of protein crystals growing in microgravity can not have improved quality are discussed. The results of this project will not only have scientific significance for establishing the mechanism through which convection affects on protein crystal growth and quality, but also lay a theoretical foundation for designing excellent environment to obtain high-quality protein crystal.

蛋白质的特殊性质和生理功能与人类疾病的治疗联系紧密，只有大量获知蛋白质分子的结构与功能才能够破解生命的奥秘和进行药物设计，而获知蛋白质分子结构的首要任务是获得高质量的蛋白质晶体。对流不可避免地存在于生长蛋白质晶体的过程中，并是影响蛋白质晶体质量的重要因素之一。微重力环境为抑制对流提供了条件，但在微重力环境下仅有少数蛋白质晶体生长实验提高了晶体质量。为了探索其原因，本项目从描述对流和扩散耦合作用下溶液中蛋白质分子运动特征数(r)出发，采用数值模拟和理论分析方法开展三方面研究工作：(1)微重力环境下各种扰动作用(重力跳动等)所引起的非稳态自然对流；(2)微重力环境下r的特性及规律；(3)比较微重力、地球表面环境下r特性及规律的异同，探索微重力环境下非稳态自然对流对蛋白质晶体生长的影响规律。项目结果不但对揭示对流对蛋白质晶体生长机理有重要科学意义，而且为设计适宜的蛋白质晶体生长环境奠定理论基础。

从描述对流和扩散耦合作用下蛋白质分子运动特征数(r)出发，采用数值模拟和理论分析的方法对对流对微重力环境下蛋白质晶体生长的影响进行研究，发展了不同微重力扰动下更为真实地蛋白质晶体生长溶液自然对流传质的研究模型,建立了高精度非稳态的数值方法，并获得了不同尺寸、不同位置、不同微重力水平以及各种微重力扰动下蛋白质生长溶液的速度场和浓度场随时间的变化规律；根据大量蛋白质晶体生长实验,揭示了蛋白质分子运动特征数对蛋白质晶体生长影响规律;分析了各种空间微重力环境下蛋白质分子运动特征数r值随时间变化规律, 并获得了不同的微重力水平所引起的对流对蛋白质晶体生长影响规律。结果表明能够稳定地保持在0.0001go量级的空间微重力环境将有利于处于容器底部蛋白质晶体的生长；空间处于高频率的阶梯型重力跳动对蛋白质晶体生长影响较大，其所引起的对流会减慢蛋白质晶体的生长速度，甚至导致蛋白质晶体停止生长。项目研究成果不仅揭示了微重力环境下蛋白质晶体生长实验失败的原因，而且为设计适宜的蛋白质晶体生长环境奠定了理论基础。项目累计发表论文3篇,已被SCI收录2篇,待发表论文3篇,参与培养硕士研究生3名.