Quantitative structure-property/activity relationship (QSPR/QSAR) model towards the prediction of novel fullerene derivatives as drug nanocarriers: the case of the CXCR7 protein and chemotherapy drugs used for breast cancer

Abstract

This project aimed to study the CXCR7 protein, related to the membrane and expressed in various forms of cancer. We will seek to calculate the binding score between breast cancer drugs and the most favorable active site in CXCR7, isolated and forming a complex with water-soluble derivatives of fullerene C60 as a nanocarrier, by molecular docking. Antitumoral drugs were tested to evaluate the behavior of the C60 to act as a drug nanocarrier. A collection of quantitative structure activity/property relationship (QSAR/QSPR) models were obtained to predict the protein-ligand binding score based on descriptors of the isolated molecules. To propose new nanomaterials that serve as drug carriers, this project proposes creating a QSPR model to predict the binding score between drugs and ligand-nanocarrier complexes. As a result of this study, it has been obtained that the binding score, when is used the fullerenes C60 or C60-COOH, has a higher magnitude in comparison with the binding score of the isolated drug. Another important conclusion is that the binding site for the isolated drugs with the CXCR7 protein is different in comparison to the drug with fullerene C60, in the first case the binding site is inside of the protein, and in the second case is outside of the protein. The case of drug-C60-COOH complex has three possible binding sites. With this project was possible to obtain mathematical models to predict the binding score between the protein and the isolated drug, the complex drug-C60, and drug-C60-COOH. In case of isolated drug, was possible to obtain a model with a MAPE (Mean Absolute Percentage Error) value of 6.17% by the use of artificial intelligence (AI). Besides, for drug-C60 complex was possible to obtain a mathematical model by multiple linear regression (MLR) with a MAPE of 4.97%. Finally, for drug-C60-COOH complex was possible to obtain a model with MAPE value of 6.7% by MLR.