This paper describes an approach to chemical data mining based on the quantitative evaluation of structural similarity. The topological fragment spectrum (TFS) method reported by the authors was used for describing a chemical structure by numerical representation. The TFS is based on enumeration and numerical characterization of all possible substructures derived from the chemical structures. The TFS was applied to similar structure searching with over 3, 600 drugs extracted from the World Drug Index. All the spectra were characterized for fragments having five or less bonds. Five different similarity (or dissimilarity) functions were investigated for their suitability for similarity searching with the TFS. Computational trial of similar structure searching on the database suggested that the present approach is successfully applicable to chemical and pharmaceutical data mining based on the evaluation of structural similarity of drug molecules.
The mechanism of the formose reaction catalyzed by thiazolium salt was investigated by MOPAC-PM3 semi-empirical molecular orbital (MO) method in order to elucidate the factor(s) stabilizing the reaction intermediates. We assumed that one factor was the formation of an ion pair with the ammonium ion in the reaction medium. Based on this assumption, possible intermediates were examined, including their structures and the heats of formation were calculated. It was suggested that the formation of an ion pair between the zwitterion intermediate (II*) and an ammonium ion and the subsequent formation of the intermediate, 2-hydroxymethyl-3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium (II**), were crucial for the reaction. A more plausible mechanism for the initial stage of the formose reaction is proposed based on calculation results.
AMBER (Assisted Model Building with Energy Refinement) is a powerful tool for simulations of bio-molecules and so on. To simulate DNA molecules with new residues that are not registered in the AMBER database, it is necessary to register them on this database by using one of the AMBER modules, PREP. However, the format of the PREP input file is very complicated, and it is hard to make by hand. Therefore, in this work, in order to make the PREP input file interactively with visualization, we add a function to our molecular structural display system, "Modrast-P". By using this function, the PREP input file can be made easily and efficiently.
A molecular modeling program for biological molecules has been developed as a 3D data-interaction tool for computational chemistry and structural bioinformatics. This program named MOLDA for Protein Modeling is written in the Java language and works multiplatform environment. MOLDA for Protein Modeling has been implemented with various functions useful for studying biological molecules by structural bioinformatics. The functions are as follows: (1) the importing function of the PDB file is implemented, (2) 3D structure of polypeptides can be generated by inputting the sequences, (3) the conformation of the polypeptide can be changed by reading the dihedral angle matrix, and (4) an amino acid residue can be changed by the point mutation operation. MOLDA for Protein Modeling is expected to be a useful tool for drug design.
PEACH, a program for molecular dynamics simulation of biochemical molecules, was transplanted from UNIX computer to Windows computer. Visual Fortran was utilized as the compiler. MD simulation of two model proteins, glucagon and prion, was performed at several different temperatures. The structures of 1AG2 and 1GCN were used as initial structures for the simulation. The helix-coil transition was observed in a few nano seconds at 400 K in the case of the glucagon model.