{"ID":2876154,"CreatedAt":"2026-06-01T04:54:23.091178241Z","UpdatedAt":"2026-06-01T04:54:23.091178241Z","DeletedAt":null,"paper_url":"https://arxiv.org/abs/2509.00684","arxiv_id":"2509.00684","title":"Valid Property-Enhanced Contrastive Learning for Targeted Optimization \u0026 Resampling for Novel Drug Design","abstract":"Efficiently steering generative models toward pharmacologically relevant regions of chemical space remains a major obstacle in molecular drug discovery under low-data regimes. We present VECTOR+: Valid-property-Enhanced Contrastive Learning for Targeted Optimization and Resampling, a framework that couples property-guided representation learning with controllable molecule generation. VECTOR+ applies to both regression and classification tasks and enables interpretable, data-efficient exploration of functional chemical space. We evaluate on two datasets: a curated PD-L1 inhibitor set (296 compounds with experimental $IC_{50}$ values) and a receptor kinase inhibitor set (2,056 molecules by binding mode). Despite limited training data, VECTOR+ generates novel, synthetically tractable candidates. Against PD-L1 (PDB 5J89), 100 of 8,374 generated molecules surpass a docking threshold of $-15.0$ kcal/mol, with the best scoring $-17.6$ kcal/mol compared to the top reference inhibitor ($-15.4$ kcal/mol). The best-performing molecules retain the conserved biphenyl pharmacophore while introducing novel motifs. Molecular dynamics (250 ns) confirm binding stability (ligand RMSD \u003c $2.5$ angstroms). VECTOR+ generalizes to kinase inhibitors, producing compounds with stronger docking scores than established drugs such as brigatinib and sorafenib. Benchmarking against JT-VAE and MolGPT across docking, novelty, uniqueness, and Tanimoto similarity highlights the superior performance of our method. These results position our work as a robust, extensible approach for property-conditioned molecular design in low-data settings, bridging contrastive learning and generative modeling for reproducible, AI-accelerated discovery.","short_abstract":"Efficiently steering generative models toward pharmacologically relevant regions of chemical space remains a major obstacle in molecular drug discovery under low-data regimes. We present VECTOR+: Valid-property-Enhanced Contrastive Learning for Targeted Optimization and Resampling, a framework that couples property-gui...","url_abs":"https://arxiv.org/abs/2509.00684","url_pdf":"https://arxiv.org/pdf/2509.00684v1","authors":"[\"Amartya Banerjee\",\"Somnath Kar\",\"Anirban Pal\",\"Debabrata Maiti\"]","published":"2025-08-31T03:55:29Z","proceeding":"cs.LG","tasks":"[\"cs.LG\",\"cs.AI\"]","methods":"[\"LoRA\",\"Generative Adversarial Network\",\"Variational Autoencoder\"]","has_code":false}