RUI: Computational Modeling of Antifreeze Proteins

本提案的目的是研究I型抗冻蛋白（AFPs）与冰的结合。结合研究的结果将用于开发一种改进的吸附抑制机制。这将通过将现代分子建模技术应用于结合在冰表面和冰/水界面的天然afp来实现。这些计算将用于研究氢键、疏水和亲水效应、盐桥和静电对afp与冰结合的影响。最重要的是要了解这些特性如何有助于抗冻蛋白的吸附-抑制特性。最初，对接程序将用于在不同的冰面上定位潜在的结合位点。一旦确定了潜在的结合位点，将使用能量最小化来确定AFP与冰表面结合的结合能。然后进行分子动力学模拟，研究防冻液在冰/水界面的相互作用，并为自由能摄动计算提供起始构型。自由能摄动模拟将用于量化单个氨基酸对结合的自由能贡献。最后，将进行布朗动力学模拟，以研究AFP和冰之间的静电如何影响AFP接近水中冰面的平移和方向转向。这项工作的结果将提供AFPs性质的定性和定量分子描述，这将有助于生物学家，化学家和生物化学家尝试“设计”更好的合成类似物。然后，这些合成的抗冻蛋白可用于保护对霜冻敏感的粮食作物、食品储存、冷冻方法和预防冻伤。总之，这项工作的数据将对化学、生物学、物理学、计算机科学和生物技术产生影响。本提案的目的是研究抗冻蛋白（AFPs）与冰之间的相互作用。这将通过将现代计算和可视化技术应用于结合在冰表面和冰/水界面上的原生AFPs来完成。这项工作的结果将提供AFPs性质的定性和定量分子描述，这将有助于生物学家，化学家和生物化学家尝试“设计”更好的合成类似物。然后，这些合成的afp可以用于保护对霜冻敏感的粮食作物、食品储存、冷冻方法、气井中的天然气水合物抑制、防止混凝土结冰和预防冻伤。总之，这项工作的数据将对化学、生物学、物理学、计算机科学、工程学和生物技术产生影响。化学系的其他教职员工将能够在他们的教学中使用该提案的结果。例如，可视化，在“实时”，一个中等大小的肽在冰/水的运动。这部“电影”将提供一种机制来描述发生的不同分子相互作用，例如氢键，溶质-溶剂相互作用，盐桥等，这些通常在课堂上作为抽象概念来讨论。＊＊＊

9322602 Madura The objective of this proposal is to investigate the binding of Type I antifreeze proteins (AFPs) to ice. The results from the binding study will then be used to develop an improved adsorption- inhibition mechanism. This will be accomplished by applying modern molecular modeling techniques on native AFPs bound to an ice surface and at the ice/water interface. These calculations will be used to study what effect hydrogen bonding, hydrophobic and hydrophilic effects, salt bridges, and electrostatics has on the binding of AFPs to ice. Most important is to understand how these properties contribute to the adsorption-inhibition nature of antifreeze proteins. Initially, a docking program will be used to locate potential binding sites on different ice surfaces. Once potential binding sites have been identified, energy minimizations will be used to determine the binding energy of the AFP bound to the ice surface. Molecular dynamics simulations will then be performed to study the interactions of the antifreeze at the ice/water interface and provide starting configurations for free energy perturbation calculations. The free energy perturbation simulations will be used to quantify the free energy contribution of individual amino acids to binding. Finally, Brownian dynamics simulations will be done to study how electrostatics, between the AFP and ice, effects the translational and orientational steering of an AFP's approach to the ice surface in water. The results from this work will provide both a qualitative and a quantitative molecular description of the properties of AFPs which will be useful to the biologist, chemist, and biochemist in their attempts to "design" better synthetic analogs. These synthetic AFPs can then be used to protect frost sensitive food crops, in food storage, in cryosurgical methods, and in the prevention of frostbite. In summary, the data from this work will have an impact in chemistry, biology, physics, compute r science, and biotechnology. %%% The objective of this proposal is to study the interactions between antifreeze proteins (AFPs) and ice. This will be accomplished by applying modern computational and visualization techniques on native AFPs bound to an ice surface and at the ice/water interface. The results from this work will provide both a qualitative and a quantitative molecular description of the properties of AFPs which will be useful to the biologist, chemist, and biochemist in their attempts to "design" better synthetic analogs. These synthetic AFPs can then be used to protect frost sensitive food crops, in food storage, in cryosurgical methods, in inhibition of gas hydrates in gas wells, in the prevention of ice formation in concrete, and in the prevention of frostbite. In summary, the data from this work will have an impact in chemistry, biology, physics, computer science, engineering, and biotechnology. Other faculty members in the Chemistry Department will be able to use the results from this proposal in their teaching. For example, visualization, in "real time", the motion of a moderately sized peptide at the ice/water. This "movie" will provide a mechanism in which to describe the different molecular interactions taking place, e.g. hydrogen bonding, solute-solvent interactions, salt- bridges and etc. which are usually discussed as abstract concepts in the classroom. ***