QSAR Modeling for Predicting Beta-Secretase 1 Inhibitory Activity in Alzheimer's Disease with Support Vector Regression

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, with the accumulation of β-amyloid (Aβ) plaques playing a key role in its progression. Beta-Secretase 1 (BACE1) is a crucial enzyme in Aβ production, making it a prime therapeutic target for AD treatment. However, designing effective BACE1 inhibitors has been challenging due to poor selectivity and limited blood-brain barrier permeability. To address these challenges, we employed a machine learning approach using Support Vector Regression (SVR) in a Quantitative Structure-Activity Relationship (QSAR) model to predict the inhibitory activity of potential BACE1 inhibitors. Our model, trained on a dataset of 7,298 compounds from the ChEMBL database, accurately predicted pIC50 values using molecular descriptors, achieving an R² of 0.690 on the testing set. The model's performance demonstrates its utility in prioritizing drug candidates, potentially accelerating drug discovery. This study highlights the effectiveness of computational approaches in optimizing drug discovery and suggests that further refinement could enhance the model’s predictive power for AD therapeutics.