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.

We have studied the dehydration process of formic acid on a TiO 2 (110) surface by using first-principles theoretical calculations. Formic acid dissociatively adsorbs to form formate and hydroxyl. It turns out that simple decomposition processes of the formate on the stoichiometric surface are energetically unfavorable. The formation of H 2 O and O vacancies from two neighboring bridging hydroxyls is relatively easy and the activation barrier is calculated to be 114 kJ/mol. On the TiO 2 (110) surface with oxygen defect sites, formate adsorbs with one O at a defect site and with the other O on a five-fold Ti, forming a bridging configuration. Further decomposition of the formate occurs through a monodentate configuration with an activation barrier of 129 kJ/mol. We have also performed STM observation corresponding to the theoretical results. It was imaged that some formates were located along the oxygen row and at an intermediate position between the oxygen row and the Ti row at elevated temperatures at which reaction takes place, indicative of the interaction between oxygen vacancy and formate. The catalytic dehydration cycle is discussed based on these results. † Part of the special issue "Gerhard Ertl Festschrift".

A number of new 4(1H)-quinazolinones were synthesized and evaluated in the carrageenin-induced paw edema test. Most of the compounds were obtained by the cyclization of the appropriately substituted anthranilamides with acid chlorides, followed by further chemical transformation. Structure-activity data suggest that 2-isopropyl-1-phenyl-, 2-cyclopropyl-1-phenyl-, and 1-isopropyl-2-phenyl-4(1H)-quinazolinones afford optimal potency and the presence of a halogen atom is preferred for activity. Adrenalectomy does not affect the antiinflammatory test results. The best result taking into account both efficacy and side effects was displayed by 1-isopropyl-(2-fluorophenyl)-4-(1H)-quinazolinone (50).