RUI: Computational Modeling of Antifreeze Proteins

9322602马都拉本提案的目的是研究I型抗冻蛋白（AFP）与冰的结合。 结合研究的结果将用于开发改进的吸附-抑制机制。 这将通过应用现代分子模拟技术对结合在冰表面和冰/水界面上的原生AFP进行模拟来实现。 这些计算将被用来研究氢键，疏水和亲水作用，盐桥和静电对AFP与冰的结合有什么影响。 最重要的是了解这些特性如何有助于抗冻蛋白的吸附抑制性质。 最初，对接程序将用于定位不同冰面上的潜在结合位点。 一旦确定了潜在的结合位点，将使用能量最小化来确定与冰表面结合的AFP的结合能。 然后进行分子动力学模拟，研究防冻剂在冰/水界面的相互作用，并提供自由能微扰计算的起始配置。 自由能扰动模拟将用于量化单个氨基酸对结合的自由能贡献。 最后，布朗动力学模拟将研究如何静电，AFP和冰之间，影响的AFP的方法在水中的冰面的平移和定向转向。 这项工作的结果将提供一个定性和定量的分子描述的性质的AFP，这将是有用的生物学家，化学家和生物化学家在他们试图“设计”更好的合成类似物。 这些人工合成的AFP可用于保护对霜冻敏感的粮食作物、食品储存、冷冻外科方法和预防冻伤。 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（AFP）和冰之间的相互作用。 这将通过应用现代计算和可视化技术对绑定到冰表面和冰/水界面的原生AFP进行研究来实现。 这项工作的结果将提供一个定性和定量的分子描述的性质的AFP，这将是有用的生物学家，化学家和生物化学家在他们试图“设计”更好的合成类似物。 这些合成的AFP然后可用于保护对霜冻敏感的粮食作物、用于食品储存、用于冷冻外科方法、用于抑制天然气威尔斯中的气体水合物、用于防止混凝土中的冰形成以及用于防止冻伤。 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。 化学系的其他教师将能够在他们的教学中使用本提案的结果。 例如，可视化，在“真实的时间”中，中等大小的肽在冰/水中的运动。 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. ***