FOCUS on NOD2: Advancing IBD Drug Discovery with a User-Informed Machine Learning Framework

Abstract

In this study, we introduce the Framework for Optimized Customizable User-Informed Synthesis (FOCUS), a generative machine learning model tailored for drug discovery. FOCUS integrates domain expertise and uses Proximal Policy Optimization (PPO) to guide Monte Carlo Tree Search (MCTS) to efficiently explore chemical space. It generates SMILES representations of potential drug candidates, optimizing for druggability and binding efficacy to NOD2, PEP, and MCT1 receptors. The model is highly interpretive, allowing for userfeedback and expert-driven adjustments based on detailed cycle reports. Employing tools like SHAP and LIME, FOCUS provides a transparent analysis of decision-making processes, emphasizing features such as docking scores and interaction fingerprints. Comparative studies with Muramyl Dipeptide (MDP) demonstrate improved interaction profiles. FOCUS merges advanced machine learning with expert insight, accelerating the drug discovery pipeline.