Miranker A, Karplus M
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
Proteins. 1991;11(1):29-34. doi: 10.1002/prot.340110104.
A new method is proposed for determining energetically favorable positions and orientations for functional groups on the surface of proteins with known three-dimensional structure. From 1,000 to 5,000 copies of a functional group are randomly placed in the site and subjected to simultaneous energy minimization and/or quenched molecular dynamics. The resulting functionality maps of a protein receptor site, which can take account of its flexibility, can be used for the analysis of protein ligand interactions and rational drug design. Application of the method to the sialic acid binding site of the influenza coat protein, hemagglutinin, yields functional group minima that correspond with those of the ligand in a cocrystal structure.
提出了一种新方法，用于确定具有已知三维结构的蛋白质表面官能团在能量上有利的位置和取向。将1000到5000个官能团随机放置在该位点，并同时进行能量最小化和/或猝灭分子动力学模拟。所得的蛋白质受体位点功能图谱能够考虑其灵活性，可用于分析蛋白质-配体相互作用及合理药物设计。将该方法应用于流感病毒包膜蛋白血凝素的唾液酸结合位点，得到的官能团极小值与共晶体结构中配体的极小值相对应。
