From SMILES to Enhanced Molecular Property Prediction: A Unified Multimodal Framework with Predicted 3D Conformers and Contrastive Learning Techniques.

Abstract

We present a novel molecular property prediction framework that requires only the SMILES format as input but is designed to be multimodal by incorporating predicted 3D conformer representations. Our model captures comprehensive molecular features by leveraging both the sequential character structure of SMILES and the three-dimensional spatial structure of conformers. The framework employs contrastive learning techniques, utilizing InfoNCE loss to align SMILES and conformer embeddings, along with task-specific loss functions, such as ConR for regression and SupCon for classification. To address data imbalance, we incorporate feature distribution smoothing (FDS), a common challenge in drug discovery. We evaluated the framework through multiple case studies, including SARS-CoV-2 drug docking score prediction, molecular property prediction using MoleculeNet data sets, and kinase inhibitor prediction for JAK-1, JAK-2, and MAPK-14 using custom data sets curated from PubChem. The results consistently outperformed state-of-the-art methods, with ConR and FDS significantly improving regression tasks and SupCon enhancing classification performance. These findings highlight the flexibility and robustness of our multimodal model, demonstrating its effectiveness across diverse molecular property prediction tasks, with promising applications in drug discovery and molecular analysis.