A Computational Study of Iron Binding at the Human H Ferritin Ferroxidase Center

该项目的目标是确定铁与铁蛋白的铁氧基酶中心之间的络合物的结构和能量。采用的主要方法将是精确的全电子密度泛函理论计算。铁蛋白是细胞内主要的铁储存蛋白，存在于从细菌到哺乳动物的各种活体细胞中。在铁氧酶反应中，Fe2+成对结合，被O2氧化成氧化铁，并被输送到蛋白质的中央空腔。因此，铁蛋白处于铁和氧调节系统的交叉点。人们对铁氧酶反应进行了深入的研究，但由于反应速度较快，结合铁络合物的结构仍未确定。将开发一个活性中心的最小模型，该模型将基于实验中发现的对铁氧化物酶活性至关重要的六种氨基酸。除了全电子密度泛函计算外，还将使用蒙特卡罗和分子动力学统计模拟来探索模型中心的势能面并定义其水合球。还将考察相邻氨基酸对模型中心和水合球体结构的影响。这项研究将在波多黎各圣胡安的大都会大学进行，参与研究的学生将是西班牙裔。该项目将扩大该大学本科生的研究范围，将分子生物学包括在内，它还将扩大生物和化学课程中引入的研究主题。波多黎各需要计算分子生物学能力。该项目将提高研究人员满足这一需求的能力，购买的计算机硬件将增强专门用于这一领域的计算设施。研究结果将广泛传播。参加UMET中学科学技术研讨会的当地高中教师将被告知项目的进展情况。

The goal of the project is to define the structures and energetics of the complexes between iron and the ferroxidase center of ferritin. The principal method employed will be accurate all-electron density functional theoretical calculations. Ferritin is the primary cellular iron-storage protein, present in the cells of living organisms from bacteria to mammals. In the ferroxidase reaction Fe2+ is bound in pairs, oxidized by O2 to iron oxide and transported to the central cavity of the protein. Ferritin, therefore, lies at the intersection of the iron and oxygen regulatory systems. The ferroxidase reaction is intensely studied, but the structures of bound iron complexes remain undefined due to the rapidity of reaction. A minimal model of the active center will be developed, which will be based on the six amino acids found experimentally to be crucial to ferroxidase activity. In addition to all-electron density functional calculations, Monte Carlo and molecular dynamics statistical simulations will be employed to explore the potential energy surface of the model center and to define its hydration sphere. The effect of neighboring amino acids on the structure of the model center and the hydration sphere will also be examined. The research will be conducted at Universidad Metropolitana in San Juan, Puerto Rico and the participating students will be Hispanic. The project will broaden the scope of undergraduate research at the university to include molecular biology and it will also widen the research themes to be introduced into courses in biology and chemistry. Computational molecular biology capability is in demand in Puerto Rico. The project will increase the abilities of the researchers to address this need, and the computer hardware purchased will enhance the computational facilities devoted exclusively to this area. The results of the research will be disseminated broadly. Local high school teachers who attend the seminar on technology in secondary-school science at UMET will be apprised of the progress of the project.