Journal of Computer Chemistry, Japan
Online ISSN : 1347-3824
Print ISSN : 1347-1767
ISSN-L : 1347-1767
10 巻 , 3 号
  • Kentaro KAWAI, Kazutaka YOSHIMARU, Yoshimasa TAKAHASHI
    2011 年 10 巻 3 号 p. 79-87
    発行日: 2011年
    公開日: 2011/12/22
    [早期公開] 公開日: 2011/11/12
    ジャーナル フリー
    In a previous study, we reported a molecular evolutionary approach for generating chemical structures. It involved a computational experiment for reproducing a target chemical structure from a seed structure by using a fitness based on the structural similarity. In this paper, we describe a method of molecular evolutionary computation using support vector machine (SVM) classifiers for generating drug-like candidate structures with specific activity. The method is based on evolutionary operations such as crossover, mutation, and selections similar to the previous study; however, the fitness of each structure was evaluated using the SVM classifiers. We performed molecular evolutionary computation using the SVM classifiers in order to generate candidate chemical structures for antihypertensive drugs of two different therapeutic classes of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP). A computer experiment to generate the ACE-selective candidates showed that evolutionary computation could favorably increase the fitness for ACE as the alternation of generations proceeded. Another computer experiment for the NEP-selective candidates also yielded a favorable result.
  • Hiroyuki TSUTSUMI, Seiji ETHO, Hazuki SHIMODA, Hirohito IKEDA, Takashi ...
    2011 年 10 巻 3 号 p. 88-97
    発行日: 2011年
    公開日: 2011/12/22
    ジャーナル フリー
    We studied the properties of an inclusion complex of amoxicillin (AMPC) in a multifunctional-modified β-cyclodextrin (mf-βCD) having an affinity for bacteria. The mf-βCDs used were βCDs modified by the introduction, on the end of a hydrocarbon chain linker, of a saccharide or urea substituent group expected to have affinity for bacteria. Using quantum chemical methods, we showed that the use of mf-βCD stabilizes AMPC against acid, and that formation of an inclusion complex should produce bacterial affinity and improve bactericidal efficiency. The chemical stabilization of AMPC by mf-βCD was tested by hydrolysis. We also showed that in order to form a 1:1 complex of AMPC and mf-βCD (AMPC-mf-βCD) functioning as a drug delivery system (DDS), the optimal conditions require mixing mf-βCD with AMPC at a molar ratio between 1:5 and 1:10 (AMPC:mf-βCD). We used Gaussian program to determine the precedence of inclusion of AMPC by mf-βCDs and to obtain optimized structures of the complex. We demonstrated the importance of orbital interactions and electronic correlations during complexation for the emergence of chemotaxis in Helicobacter pylori1) toward the urea substituent on mf-βCDs. We further used the self-consistent reaction field (SCRF) method to study the effects of solvent. Using the optimized structures under solvent-free conditions, we calculated the energies of each AMPC-mf-βCD complex in water by the SCRF method using B3LYP/6-31G* levels.
  • Yosuke KATAOKA, Yuri YAMADA
    2011 年 10 巻 3 号 p. 98-104
    発行日: 2011年
    公開日: 2011/12/22
    ジャーナル フリー
    An equation of state for a perfect solid is proposed, where the system includes only single spherical molecules. A Lennard-Jones interaction is assumed in the nearest neighbors on the face-centered cubic (FCC) lattice. The internal energy is the sum of the average kinetic energy and the potential energy at 0 K, which is a function of the volume. The pressure satisfies the thermodynamic conditions for the internal energy and pressure. The equilibrium condition is solved numerically for the solid-gas equilibrium of argon. The Gibbs energy gives a reasonable vapor pressure for solid argon, if the temperature dependence of the virial term is taken into account.