VISCANA: Visualized cluster analysis of protein-ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening
VISCANA: Visualized cluster analysis of protein-ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening
复制标题
DOI：
10.1021/ci050262q
复制
发表时间：
2006-01-01
影响因子：
5.6
通讯作者：
Nakano, T
中科院分区：
文献类型：
--
作者：
Amari, S;Aizawa, M;Nakano, T
我们发展了一种蛋白质-配体相互作用的可视化聚类分析(VISCANA)，它基于用于虚拟配体筛选的量子理论来分析受体和配体相互作用的模式。Kitaura等人。(化学。太棒了。让我们来吧。1999、312、319-324。)提出了一种从头算片段分子轨道(FMO)方法，利用该方法可以很容易地以化学精度处理蛋白质等大分子。在FMO方法中，分子的总能量是通过碎片能量和碎片间相互作用能(ICIES)之和来计算的。在本文中，我们提出了一种使用相异度的聚类分析方法，相异度被定义为两个配体之间的欧几里得距离的平方。尽管通过聚类得到的有序表的结果仍然是大量的数字集合，但我们将聚类方法与iTIMS的图形表示相结合，通过用能够定量和定性地反映iTIMS的颜色来表示每个数据点。我们将VISCANA应用于人类雌激素受体α配体结合域(57个氨基酸残基)的药效团的对接研究。通过VISCANA，我们可以根据配体与受体蛋白的氨基酸残基的相互作用模式，将结构不同的配体分类为功能相似的簇。此外，VISCANA可以通过对接计算分析某些构象的受体-配体相互作用的模式来估计正确的对接构象。
We have developed a visualized cluster analysis of protein-ligand interaction (VISCANA) that analyzes the pattern of the interaction of the receptor and ligand on the basis of quantum theory for virtual ligand screening. Kitaura et al. (Chem. Phys. Lett. 1999, 312, 319-324.) have proposed an ab initio fragment molecular orbital (FMO) method by which large molecules such as proteins can be easily treated with chemical accuracy. In the FMO method, a total energy of the molecule is evaluated by summation of fragment energies and interfragment interaction energies (IFIEs). In this paper, we have proposed a cluster analysis using the dissimilarity that is defined as the squared Euclidean distance between IFIEs of two ligands. Although the result of an ordered table by clustering is still a massive collection of numbers, we combine a clustering method with a graphical representation of the IFIEs by representing each data point with colors that quantitatively and qualitatively reflect the IFIEs. We applied VISCANA to a docking study of pharmacophores of the human estrogen receptor alpha ligand-binding domain (57 amino acid residues). By using VISCANA, we could classify even structurally different ligands into functionally similar clusters according to the interaction pattern of a ligand and amino acid residues of the receptor protein. In addition, VISCANA could estimate the correct docking conformation by analyzing patterns of the receptor-ligand interactions of some conformations through the docking calculation.