title: VISCANA: visualized cluster analysis of protein-ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening.
abstract: 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.
authors.affiliation: Collaborative Research Center of Frontier Simulation Software for Industrial Science, Institute of Industrial Science, University of Tokyo, Meguro-ku, Japan. samari@fsis.iis.u-tokyo.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Amari
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aizawa
authors.forename: Junwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Kaori
authors.initials: K
authors.lastname: Fukuzawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Iwasawa
authors.forename: Kotoko
authors.initials: K
authors.lastname: Nakata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Chuman
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakano
mesh_terms: D001665:Binding Sites; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012984:Software
chemical_list: D047628:Estrogen Receptor alpha; D008024:Ligands