Quantitative structure-activity relationship modeling of insect juvenile hormone activity of 2,4-dienoates using computed molecular descriptors

Abstract

Juvenile hormone (JH) activity of one hundred and eighty 2,4-dienoates reported for the larvae/pupae of six insect species was modeled using 915 atom pairs and 258 global molecular descriptors (topological and geometrical). Ridge regression, principal component regression and partial least square regression methods were used to model each of the JH activities. The use of all of the available parameters did not yield any good models, and extensive predictor trimming was necessary to improve the models. Ridge regression was found to give the best results among the three statistical tools used. The top ten molecular descriptors selected based on the t-statistic for each of the six models were found to be mostly atom pairs containing heteroatoms and topochemical descriptors. This suggests the importance of the chemical nature of the ligand rather than mere space-filling as the basis of the JH bioactivity. The residual plots indicate the existence of some non-linear relations, and recursive partitioning was used to capture any nonlinear relation between the bioassays and the molecular descriptors.

Keywords:

• QSAR
• Juvenile hormone mimic
• Molecular descriptors
• 2,4-dienoates
• Variable selection

Acknowledgments

This paper represents contribution number 387 from the Center for Water and the Environment of the Natural Resources Research Institute. This research is funded by United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement 58-1275-4-313.

This paper was presented in the 4th INDO-US workshop on mathematical chemistry, January 8–12, 2005, University of Pune, Pune, India.