VISCANA: Visualized cluster analysis of protein - Ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening

Shinji Amari, Masahiro Aizawa, Junwei Zhang, Kaori Fukuzawa, Yuji Mochizuki, Yoshio Iwasawa, Kotoko Nakata, Hiroshi Chuman, Tatsuya Nakano

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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, 572, 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 a 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.

Original languageEnglish
Pages (from-to)221-230
Number of pages10
JournalJournal of chemical information and modeling
Volume46
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

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