53.
Kiralj R., Ferreira M. M. C., “A priori molecular descriptors in QSAR: a case of HIV-1 protease inhibitors. I. The Chemometric approach”. J. Mol. Graph. Mod., 21(5), 435-448 (Mar 2003).
[Special issue including a special section "Challenges for Drug Discovery and Development in the Twenty-first Century" with five contribution from the biomedical section (Theme C) of the IUPAC World Congress held 1-6 July in Brisbane, Queensland, Australia. This issue was completed with relevant articles of other scientists in this field, that did not participate the IUPAC meeting. See Notes. Article selected for the Abstract Sevice of the QSAR Comb. Sci. journal, see Selected.]
[Article.]
 

Abstract.
A quantitative structure-activity relationship (QSAR) study on 48 peptidic HIV-1 protease inhibitors was performed. Fourteen a priori molecular descriptors were used to build QSAR models. Hierarchical cluster analysis (HCA), principal component analysis (PCA) and partial least squares regression (PLS) were employed. PLS models with 32/16 (model I) and 48/0 (model II) molecules in the training/external validation set were constructed. The a priori molecular descriptors were related to two energetic variables using PLS. HCA and PCA on data from model II classified the inhibitors as slightly, moderately and highly active; three principal components, the chemical nature of which has been highlighted, are enough to describe the enzyme-inhibitor binding. Model I (r2=0.91, q2=0.84) is comparable to literature models obtained by various QSAR softwares, which justified the use of a priori descriptors.

Keywords.
A priori molecular descriptors; QSAR; HIV-1 protease inhibitors; Chemometrics

Keywords Plus.