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.

Fragmentation Methods: A Route to Accurate Calculations on Large Systems

“…In 2006, Amari et al 299 developed the visualized cluster analysis of proteinÀligand interactions based on the FMO method. Du and Sakurai 300 in 2010 proposed a multivariate analysis of properties of amino acid residues.…”

A Preliminary Study of Correction for Inter Fragment Interaction Energy (IFIE) between Fragments Sharing Bond Detached Atom (BDA)

“…, 渡邉千鶴 その有効性が広く認識されている [1][2][3][4][5][6][7]。FMO法の特 徴として、系を分割したフラグメント間の相互作用 エネルギーinter fragment interaction energy (IFIE) [8,9] （GAMESS版FMO法 [10] …”

Explicit solvation of a single-stranded DNA, a binding protein, and their complex: a suitable protocol for fragment molecular orbital calculation

“…The net charges of the solutes were calculated as summations of the net charges of the constituent atoms obtained by either Mulliken population analysis (MPA) or natural population analysis (NPA) [35]. Interaction energies within the solvated systems were calculated based on inter-fragment interaction energy analysis (IFIE) [34,36,37]. In FMO2, the total energy of the system (E) is obtained as the sum of internal-fragment energies (E' I , I=1, ..., N) and inter-fragment energies (ΔE IJ , I<J) as follows:…”