A Quantitative Structure-Activity Relationship for Human Plasma Protein Binding: Prediction, Validation and Applicability Domain.

Abstract

The purpose of this study was to develop a robust and externally predictive in silico QSAR-neural network model for predicting plasma protein binding of drugs. This model aims to enhance drug discovery processes by reducing the need for chemical synthesis and extensive laboratory testing. A dataset of 277 drugs was used to develop the QSAR-neural network model. The model was constructed using a Filter method to select 55 molecular descriptors. The validation set's external accuracy was assessed through the predictive squared correlation coefficient Q2 and the root mean squared error (RMSE). The developed QSAR-neural network model demonstrated robustness and good applicability domain. The external accuracy of the validation set was high, with a predictive squared correlation coefficient Q2 of 0.966 and a root mean squared error (RMSE) of 0.063. Comparatively, this model outperformed previously published models in the literature. The study successfully developed an advanced QSAR-neural network model capable of predicting plasma protein binding in human plasma for a diverse set of 277 drugs. This model's accuracy and robustness make it a valuable tool in drug discovery, potentially reducing the need for resource-intensive chemical synthesis and laboratory testing.