iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

Détails

ID Serval
serval:BIB_7C3EBBDEAC5D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.
Périodique
Journal of Chemical Information and Modeling
Auteur⸱e⸱s
Daina A., Michielin O., Zoete V.
ISSN
1549-960X (Electronic)
ISSN-L
1549-9596
Statut éditorial
Publié
Date de publication
2014
Volume
54
Numéro
12
Pages
3284-3301
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.
Pubmed
Web of science
Création de la notice
29/01/2015 21:27
Dernière modification de la notice
20/08/2019 15:37
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