DOCKING PROTEIN DENSITIES

蛋白质组装体的结构在很大程度上是由非共价键决定的。 蛋白质之间的相互作用。 形状互补的重要性 相互作用的分子表面是公认的，但不是 容易研究，由于难以量化的形状。 这项建议 将开发用于（1）表征蛋白质形状的方法 表面，和（2）预测已知的三种蛋白质之间的复合物- 空间结构 这些方法将被设计成有效的，即使 表面氨基酸侧链具有不确定取向， 这在蛋白质晶体学研究中经常发生。 构象 灵活性将被建模为三层的部分占用（密度）， 三维网格 侧链的平均密度将用于 形状测量 一个可靠的蛋白质对接计算机程序将是 一种更快、更便宜的研究蛋白质关联的方法， 配合物的X射线晶体学实验研究。 应用包括：（a）预测单克隆抗体如何结合至 其蛋白抗原，（B）将病毒外壳蛋白单体组装成 衣壳，和（c）遗传疾病镰状细胞贫血，其中血红蛋白 单体以不正确的方式缔合。 开发的软件将 授权给学术、政府和行业科学家研究 疾病的分子基础

The structure of protein assemblies is largely determined by non-covalent interactions between proteins. The importance of shape complementarity of interacting molecular surfaces is generally recognized, but is not easily studied, due to difficulties in quantifying shape. This proposal will develop methods for (1) characterizing the shape of protein surfaces, and (2) predicting complexes between proteins of known three- dimensional structure. The methods will be designed to work, even if the surface amino acid side chains have indeterminate orientation, as is often the case in protein crystallographic studies. Conformational flexibility will be modeled as partial occupancy (density) on a three- dimensional grid. The side chains' averaged density will be used for shape measurement. A reliable protein-docking computer program will be a quicker and less expensive means to study a protein association than an X-ray crystallographic experimental study of the complex. Applications include: (a) predicting how a monoclonal antibody binds to its protein antigen, (b) the assembly of viral coat protein monomers into capsids, and (c) the genetic disease sickle cell anemia, where hemoglobin monomers associate in an incorrect way. The software developed will be licensed to academic, governmental and industry scientists researching the molecular basis of disease.