DOCKING PROTEIN DENSITIES

拟议研究的目的是开发计算机方法来 预测蛋白质复合体的三维结构，给定 单个蛋白质组分的三维结构。一个 这项工作的特别目标是考虑到有一个事实 蛋白质表面的一些构象变化，这是由于 表面的原子。每种蛋白质都由一个立方体表示 占用面积或密度的点阵，介于0.0和 1.0描述该多维数据集有多少时间被 蛋白质的原子。对于蛋白质内部的立方体，密度 将为1.0。将分析这些柔软或模糊表面的形状， 互补的形状将在计算机中对接在一起。 蛋白质-蛋白质对接预测在(1)组装中应该是有用的 病毒外壳蛋白单体进入衣壳，(2)遗传病 镰状细胞性贫血，即出现不想要的血红蛋白聚合 亚基，(3)了解抗体-抗原识别，(4) 了解蛋白质毒素的机制，如白喉和 霍乱毒素，以及(5)设计蛋白质药物。 拟议的商业应用：期间开发的计算机软件 该项目将被授权给制药和生物技术公司。 用于设计用作药物的蛋白质的公司。 它还将以更低的费用被授权给大学和 研究机构。

The purpose of the proposed research is to develop computer methods to predict the three-dimensional structures of protein complexes, given the three-dimensional structures of the individual protein components. A special goal of this work is to take into account the fact that there is some conformational variation at protein surfaces, due to the motions of the atoms at the surface. Each protein is represented by a cubical lattice of occupancies or densities, which are numbers between 0.0 and 1.0 describing how much of the time that cube is occupied by the protein's atoms. For cubes in the interior of the protein, the densities will be 1.0. The shapes of these soft or fuzzy surfaces will be analyzed, and complementary shapes will be docked together in the computer. Protein-protein docking predictions should be useful in (1) the assembly of viral coat protein monomers into capsids, (2) the genetic disease sickle cell anemia, where there is unwanted polymerization of hemoglobin subunits, (3) understanding antibody-antigen recognition, (4) understanding the mechanisms of protein toxins, such as diphtheria and cholera toxins, and (5) designing protein drugs. PROPOSED COMMERCIAL APPLICATION: The computer software developed during this project will be licensed to pharmaceutical and biotechnology companies for use in designing proteins to be used as pharmaceuticals. It will also be licensed, for a more modest fee, to universities and research institutes.