2002 Volume 3 Pages 63-72
In 3D-QSAR analysis such as comparative molecular field analysis (CoMFA), proper superimposition of molecules is required. Since appropriate superimposition is important factor for construction of predictive data-model and correct analysis of it, various methodologies for molecular alignment have been proposed. We have proposed novel molecular alignment method using Hopfield Neural Network (HNN) [M. Arakawa, K. Hasegawa, K. Funatsu, Journal of Computer Aided Chemistry, 2, 29-36 (2001)]. In this paper, 3D-QSAR analysis of Cyclooxygenase-2 (COX-2) inhibitors which consist of three different types of skeleton, is reported. The structures of COX-2 inhibitors were aligned using our HNN method and analyzed by CoMFA. A robust PLS model (R²=0.922, Q²=0.653) was obtained and it was validated by contour map of the regression coefficients and X-ray crystal structure of COX-2.
