Concept-Driven Deep Learning for Enhanced Protein-Specific Molecular Generation

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations: those operating at the atomic level often lack synthetic feasibility, drug-likeness, and interpretability, while fragment-based approaches frequently overlook comprehensive factors that influence protein-molecule interactions. To address these challenges, we propose a novel fragment-based molecular generation framework tailored for specific proteins. Our method begins by constructing a protein subpocket and molecular arm concept-based neural network, which systematically integrates interaction force information and geometric complementarity to sample molecular arms for specific protein subpockets. Subsequently, we introduce a diffusion model to generate molecular backbones that connect these arms, ensuring structural integrity and chemical diversity. Our approach significantly improves synthetic feasibility and binding affinity, with a 4% increase in drug-likeness and a 6% improvement in synthetic feasibility. Furthermore, by integrating explicit interaction data through a concept-based model, our framework enhances interpretability, offering valuable insights into the molecular design process.

The Impact of Domain Knowledge and Multi-Modality on Intelligent Molecular Property Prediction: A Systematic Survey

The precise prediction of molecular properties is essential for advancements in drug development, particularly in virtual screening and compound optimization. The recent introduction of numerous deep learning-based methods has shown remarkable potential in enhancing molecular property prediction (MPP), especially improving accuracy and insights into molecular structures. Yet, two critical questions arise: does the integration of domain knowledge augment the accuracy of molecular property prediction and does employing multi-modal data fusion yield more precise results than unique data source methods? To explore these matters, we comprehensively review and quantitatively analyze recent deep learning methods based on various benchmarks. We discover that integrating molecular information will improve both MPP regression and classification tasks by upto 3.98% and 1.72%, respectively. We also discover that the utilizing 3-dimensional information with 1-dimensional and 2-dimensional information simultaneously can substantially enhance MPP upto 4.2%. The two consolidated insights offer crucial guidance for future advancements in drug discovery.

3D-Mol: A Novel Contrastive Learning Framework for Molecular Property Prediction with 3D Information

Molecular property prediction offers an effective and efficient approach for early screening and optimization of drug candidates. Although deep learning based methods have made notable progress, most existing works still do not fully utilize 3D spatial information. This can lead to a single molecular representation representing multiple actual molecules. To address these issues, we propose a novel 3D structure-based molecular modeling method named 3D-Mol. In order to accurately represent complete spatial structure, we design a novel encoder to extract 3D features by deconstructing the molecules into three geometric graphs. In addition, we use 20M unlabeled data to pretrain our model by contrastive learning. We consider conformations with the same topological structure as positive pairs and the opposites as negative pairs, while the weight is determined by the dissimilarity between the conformations. We compare 3D-Mol with various state-of-the-art (SOTA) baselines on 7 benchmarks and demonstrate our outstanding performance in 5 benchmarks.