title: AutoGPA: An Automated 3D-QSAR Method Based on Pharmacophore Alignment and Grid Potential Analysis.
abstract: 3D-QSAR approach has been widely applied and proven to be useful in the case where no reliable crystal structure of the complex between a biologically active molecule and the receptor is available. At the same time, however, it also has highlighted the sensitivity of this approach. The main requirement of the traditional 3D-QSAR method is that molecules should be correctly overlaid in what is assumed to be the bioactive conformation. Identifying an active conformation of a flexible molecule is technically difficult. It has been a bottleneck in the application of the 3D-QSAR method. We have developed a 3D-QSAR software named AutoGPA especially based on an automatic pharmacophore alignment method in order to overcome this problem which has discouraged general medicinal chemists from applying the 3D-QSAR methods to their "real-world" problems. Applications of AutoGPA to three inhibitor-receptor systems have demonstrated that without any prior information about the three-dimensional structure of the bioactive conformations AutoGPA can automatically generate reliable 3D-QSAR models. In this paper, the concept of AutoGPA and the application results will be described.
authors.affiliation: Science and Technology Systems Division, Computational Science Department, Ryoka Systems Inc., 1-28-38 Shinkawa, Chuo-ku, Tokyo 104-0033, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Asakawa
authors.affiliation: Science and Technology Systems Division, Computational Science Department, Ryoka Systems Inc., 1-28-38 Shinkawa, Chuo-ku, Tokyo 104-0033, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Science and Technology Systems Division, Computational Science Department, Ryoka Systems Inc., 1-28-38 Shinkawa, Chuo-ku, Tokyo 104-0033, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Goto
authors.affiliation: Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Hirayama