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

Abstract EN

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.