A three-dimensional receptor model for isovanillic sweet derivatives

Abstract

Using pseudoreceptor modelling, we have derived a three-dimensional binding-site model for the structurally uncharacterised sweet-taste receptor. The receptor model was derived based on 17 sweet compounds of the isovanillyl class (4-methoxy-3-hydroxybenzyl) as the training set and consists of nine key amino-acid residues embedded in a hydrophobic receptor cavity. The underlying technology (software PrGen) allows for a dynamical treatment of the ligand–receptor complex (ligand equilibration and Monte-Carlo scanning of receptor space) as well as for receptor-mediated ligand alignment. Free energies of ligand binding are estimated based on ligand–receptor interactions, ligand desolvation energy, change of ligand internal energy and change of ligand entropy upon receptor binding.