QSAR Classification Models for Predicting the Activity of Inhibitors of Beta-Secretase (BACE1) Associated with Alzheimer’s Disease

PONZONI, IGNACIO; ROCA, CARLOS; VAZQUEZ, GUSTAVO E.; CAMPILLO, NURIA E.; MARTÍNEZ, MARÍA J.; CRAVERO, FIORELLA; DÍAZ, MÓNICA F.; SEBASTIÁN-PÉREZ, VÍCTOR; DE LA CRUZ PÉREZ, CARLOS; PÁEZ, JUAN A.; PONZONI, IGNACIO; ROCA, CARLOS; VAZQUEZ, GUSTAVO E.; CAMPILLO, NURIA E.; MARTÍNEZ, MARÍA J.; CRAVERO, FIORELLA; DÍAZ, MÓNICA F.; SEBASTIÁN-PÉREZ, VÍCTOR; DE LA CRUZ PÉREZ, CARLOS; PÁEZ, JUAN A.

Scientific Reports

Springer Nature Publishing AG

Lugar: Berlin; Año: 2019 vol. 9 p. 1 - 13

Alzheimer`s disease is one of the most common neurodegenerative disorders in elder population. The β-site amyloid cleavage enzyme 1 (BACE1) is the major constituent of amyloid plaques and plays a central role in this brain pathogenesis, thus it constitutes an auspicious pharmacological target for its treatment. In this paper, a QSAR model for identification of potential inhibitors of BACE1 protein is designed by using classification methods. For building this model, a database with 215 molecules collected from different sources has been assembled. This dataset contains diverse compounds with different scaffolds and physical-chemical properties, covering a wide chemical space in the drug-like range. The most distinctive aspect of the applied QSAR strategy is the combination of hybridization with backward elimination of models, which contributes to improve the quality of the final QSAR model. Another relevant step is the visual analysis of the molecular descriptors that allows guaranteeing the absence of information redundancy in the model. The QSAR model performances have been assessed by traditional metrics, and the final proposed model has low cardinality, and reaches a high percentage of chemical compounds correctly classified.