Comparison of various methods for validity evaluation of QSAR models

BACKGROUND: Quantitative structure–activity relationship (QSAR) modeling is one of the most important computational tools employed in drug discovery and development. The external validation of QSAR models is the main point to check the reliability of developed models for the prediction activity of not yet synthesized compounds. It was performed by different criteria in the literature. METHODS: In this study, 44 reported QSAR models for biologically active compounds reported in scientific papers were collected. Various statistical parameters of external validation of a QSAR model were calculated, and the results were discussed. RESULTS: The findings revealed that employing the coefficient of determination (r(2)) alone could not indicate the validity of a QSAR model. The established criteria for external validation have some advantages and disadvantages which should be considered in QSAR studies. CONCLUSION: This study showed that these methods alone are not only enough to indicate the validity/invalidity of a QSAR model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13065-022-00856-4.