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Adv Pharm Bull. 2023;13(4): 784-791.
doi: 10.34172/apb.2023.078
PMID: 38022813
PMCID: PMC10676552
  Abstract View: 519
  PDF Download: 375

Research Article

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

Affaf Khaouane 1* ORCID logo, Samira Ferhat 1 ORCID logo, Salah Hanini 1 ORCID logo

1 Laboratory of Biomaterial and transport Phenomena (LBMPT), University of Médéa, pole urbain, 26000, Médéa, Algeria.
*Corresponding Author: Affaf Khaouane, Email: affoufa80@gmail.com

Abstract

Purpose: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

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Submitted: 24 May 2022
Revision: 23 Jan 2023
Accepted: 24 Apr 2023
ePublished: 29 Apr 2023
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