CORAL: Monte Carlo based global QSAR modelling of Bruton tyrosine kinase inhibitors using hybrid descriptors

ABSTRACT

Global QSAR modelling was performed to predict the pIC₅₀ values of 233 diverse heterocyclic compounds as BTK inhibitors with the Monte Carlo algorithm of CORAL software using the DCW hybrid descriptors extracted from SMILES notations of molecules. The dataset of 233 BTK inhibitors was randomly split into training, invisible training, calibration and validation sets. The index of ideality of correlation was also applied to build and judge the predictability of the QSAR models. Eight global QSAR models based on the hybrid optimal descriptor using two target functions, i.e. TF₁ (W_IIC = 0) and TF₂ (W_IIC = 0.2) have been constructed. The statistical parameters of QSAR models computed by TF₂ are more reliable and robust and were used to predict the pIC₅₀ values. The model constructed for split 4 via TF₂ is regarded as the best model and the numerical values of r²_Train, r²_Valid, Q²_Train and Q²_Valid are equal to 0.7981, 0.7429, 0.7898 and 0.6784, respectively. By internal and external validation techniques, the predictability and reliability of the designed models have been assessed. The structural attributes responsible for the increase and decrease of pIC₅₀ of BTK inhibitors were also identified.

KEYWORDS:

• Global QSAR
• BTK inhibitors
• CORAL software
• SMILES
• Monte Carlo method

Acknowledgements

The authors are thankful to Dr. Andrey A. Toropov and Dr. Alla P. Toropova for providing CORAL software. The authors are also thankful to their respective universities for providing the infrastructure.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2021.2003429

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.