Benchmarking of QSAR models for blood-brain barrier permeation

Journal Publication ResearchOnline@JCU
Konovalov, Dmitry A.;Coomans, Danny;Deconinck, Eric;Vander Heyden, Yvan
Abstract

Using the largest available database of 328 blood-brain distribution (logBB) values, a quantitative benchmark was proposed to allow for a consistent comparison of the predictive accuracy of current and future logBB/ quantitative structure-activity relationship (-QSAR) models. The usefulness of the benchmark was illustrated by comparing the global and k-nearest neighbors (kNN) multiple-linear regression (MLR) models based on the linear free-energy relationship (LFER) descriptors, and one non-LFER-based MLR model. The leaveone-out (LOO) and leave-group-out Monte Carlo (MC) cross-validation results (q2 ) 0.766, qms ) 0.290, and qmsmc ) 0.311) indicated that the LFER-based kNN-MLR model was currently one of the most accurate predictive logBB-QSAR models. The LOO, MC, and kNN-MLR methods have been implemented in the QSAR-BENCH program, which is freely available from www.dmitrykonovalov.org for academic use.

Journal

Journal of Chemical Information and Modeling

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47

ISBN/ISSN

1549-960X

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4

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Publisher

American Chemical Society

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DOI

10.1021/ci700100f