AutoGPA : An Automated 3D-QSAR Method Based on Pharmacophore Alignment and Grid Potential Analysis

• Published in: International Journal of Medicinal Chemistry (Online) 2012-01, Vol.2012 (2012), p.1-9
• Main Authors: Asakawa, Naoyuki, Kobayashi, Seiichi, Goto, Junichi, Hirayama, Noriaki
• Format: Article
• Language: English
• ISSN: 2090-2069; 2090-2077
• DOI: 10.1155/2012/498931

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.