Structure-based analysis of the ultraspiracle protein and docking studies of putative ligands

The ultraspiracle protein (USP) is the insect ortholog of the mammalian retinoid X receptor (RXR). Fundamental questions concern the functional role of USP as the heterodimerization partner of insect nuclear receptors such as the ecdysone receptor. The crystallographic structures of the ligand binding domain of USPs of Heliothis virescens and Drosophila melanogaster solved recently show that helix 12 is locked in an antagonist conformation raising the question whether USPs could adopt an agonist conformation as observed in RXRα. In order to investigate this hypothesis, a homology model for USP is proposed that allows a structural analysis of the agonist conformation of helix 12 based on the sequence comparison with RXR. For USP, one of the main issues concerns its function and in particular whether its activity is ligand independent or not. The x-ray structures strongly suggest that USP can bind ligands. Putative ligands have therefore been docked in the USP homology model. Juvenile hormones and juvenile hormone analogs were chosen as target ligands for the docking study. The interaction between the ligand and the receptor are examined in terms of the pocket shape as well as in terms of the chemical nature of the residues lining the ligand binding cavity

Test d’une hypothèse d’investissement à écarts multiples

According to the multiple-gap hypothesis, investment decisions, determined by the joint action of multiple determinants, result from the dominance at the time of the decision of the most constraining of these factors. This hypothesis is tested on Dutch investment data for the period 1951-1974 by means of three types of models: a "rigid" model in which a single regime is selected at any time, and two "flexible" models allowing for a joint action of the various determinants, the last model incorporating a switching mechanism with respect to the dominant factor. Estimation problems are discussed and the results obtained with the different models are compared