3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors: application of molecular field analysis |
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Authors: | Nunthanavanit Patcharawee Anthony Nahoum G Johnston Blair F Mackay Simon P Ungwitayatorn Jiraporn |
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Affiliation: | Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok, Thailand. |
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Abstract: | Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for chromone derivatives against HIV-1 protease using molecular field analysis (MFA) with genetic partial least square algorithms (G/PLS). Three different alignment methods: field fit, pharmacophore-based, and receptor-based were used to derive three MFA models. All models produced good predictive ability with high cross-validated r(2) (r(2) (cv)), conventional r(2), and predictive r(2)(r(2)(pred)) values. The receptor-based MFA showed the best statistical results with r(2) (cv) = 0.789, r(2)= 0.886, and r(2)(pred) = 0.995. The result obtained from the receptor-based model was compared with the docking simulation of the most active compound 21 in this chromone series to the binding pocket of HIV-1 protease (PDB entry 1AJX). It was shown that the MFA model related well with the binding structure of the complex and can provide guidelines to design more potent HIV-1 protease inhibitors. |
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Keywords: | Alignment Chromone derivatives HIV‐1 protease Molecular field analysis (MFA) 3D‐QSAR |
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