A three-dimensional receptor model for isovanillic sweet derivatives
A three-dimensional receptor model for isovanillic sweet derivatives
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DOI：
10.1039/a709167b
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发表时间：
1998-06-01
期刊：
影响因子：
--
通讯作者：
Vedani, A
中科院分区：
文献类型：
--
作者：
Bassoli, A;Merlini, L;Vedani, A
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.The validity of the receptor model has been assessed by using a test set of eight isovanillyl sweet compounds different from the training set, For these ligands, the obtained binding-site surrogate is capable of predicting free energies of ligand binding, Delta G degrees, to within 0.99 kcal mol(-1) (rms) of their experimental value, corresponding to an uncertainty in the sweetness of a factor of 5.5, Maximal individual errors of predicted sweetnesses do not exceed a factor of 18.
