Investigations of the Contribution of Nonpolar Interactions to Molecular Recognition and Binding at Liquid-Crystal Interfaces

在化学学部分析和表面化学项目以及极地项目办公室北极和南极项目的支持下，南阿拉巴马大学的Andrzej Wierzbicki教授和杜肯大学的Jeffy Madura教授组成的合作团队正在研究I型抗冻蛋白（AFPs）作用机制中的结构-功能关系。本研究的具体目的是阐明非极性相互作用对分子识别和结合的贡献的重要性。I型afp是一种小的α -螺旋蛋白，通过冰点降低的非累加机制保护某些鱼类免受冷冻。这种保护机制依赖于这些蛋白质微妙的功能设计，巧妙地利用极性和非极性残基来最小化水/冰界面区域的自由能。合作者使用分子动力学模拟来研究各种分子相互作用，包括疏水和亲水性，这些相互作用会影响水/冰界面上afp的识别和结合。平均力势法将用于直接计算水/冰界面处I型原子力能谱的吉布斯自由能。更广泛的分子机制，通过AFPs抑制冰的生长，并与磷脂膜相互作用也将被研究，以阐明AFPs如何保护生物体免受冻结。在计算研究的基础上，将设计和实验测试功能性AFP类似物，以研究非极性相互作用对水/冰界面分子识别和结合的重要性。这些研究对包括农业、医药、飞机、石油和天然气勘探和精炼在内的各个领域都有潜在的影响。它们将通过为毕业生和本科生提供新颖的研究经验，提供多学科科学方面的培训和教育。他们将鼓励、激励和培养下一代化学家将最先进的计算和实验方法整合到他们的研究技能和工具中。具体来说，每年至少有3名本科生将接受综合实验和计算方法的培训，以研究科学中的跨学科问题。

ABSTRACT CHE-0616674Wierzbicki/South AlabamaWith support from the Analytical and Surface Chemistry Program in the Division of Chemistry, and the Arctic and Antarctic Programs in the Office of Polar Programs, a collaborative team involving the groups of Prof. Andrzej Wierzbicki at the University of South Alabama and Prof. Jeffy Madura at Duquesne University is studying structure-function relationships in the mechanism of action of Type I antifreeze proteins (AFPs). The specific aim of this research is to elucidate the importance of the contribution of nonpolar interactions to molecular recognition and binding. The Type I AFPs are small alpha-helical proteins which protect certain species of fish from freezing by a non-colligative mechanism of freezing point depression. This protective mechanism relies on the subtle functional design of these proteins which masterfully utilizes both polar and nonpolar residues to minimize the free energy at the water/ice interfacial region. The collaborators use molecular dynamics simulations to study the various molecular interactions, both hydrophobic and hydrophilic, that influence the recognition and binding of AFPs at water/ice interfaces. The potential of mean force method will be used for direct computation of the Gibbs free energies of Type I AFPs at the water/ice interfaces. The broader molecular mechanism by which AFPs inhibit the growth of ice and interact with phospholipid membranes will be also studied to elucidate how the AFPs protect living organisms from freezing. Based on the computational studies, functional AFP analogues will be designed and experimentally tested to investigate the importance of nonpolar interactions for molecular recognition and binding at water/ice interfaces.These studies have the potential for impact in diverse fields including agriculture, medicine, aircraft, and oil and gas exploration and refining. They will provide for training and education in multidisciplinary sciences by providing a novel research experience for graduates and undergraduates. They will encourage, motivate, and nurture the next generation of chemists to integrate state-of-the-art computational and experimental methods into their repertoire of research skills and tools. Specifically a minimum of 3 undergraduates will be trained each year in the integration of experimental and computational methods to study interdisciplinary problems in science.