QSAR and primary docking studies of trans-stilbene (TSB) series of imaging agents for β-amyloid plaques

In vivo imaging β-amyloid plaques can help to diagnose Alzheimer's disease (AD). Some trans-stilbene derivatives are hopeful as probes for in vivo evaluation of β-amyloid plaques. In order to explore the interaction mechanism, quantitative structure-activity relationship (QSAR) and molecular docking studies were performed on trans-stilbene (TSB) compounds. First, 22 TSB-based analogues were optimized using DFT method. Through QSAR analysis, highly predictive QSAR model was developed with r2 value of 0.857. Based on the QSAR model, one possible binding site was proposed and validated by molecular docking studies. The Lamarckian Genetic Algorithm (LGA) was applied to deal with the ligand-protein interactions. A good correlation between the calculated binding energies and the experimental binding affinities suggests that the identified binding site is reliable. The QSAR model and the information of the ligand-protein interaction would be useful in developing new imaging agents for β-amyloid plaques.