ChemRxiv · 2022 · 83 citations · 78 references
PharmacyMedicinal ChemistryComputational ChemistryDrug DesignDrug DiscoveryChemical Space ExplorationMolecular DescriptorsMolecular DockingMolecular ModelingProtein Structure ModelingProtein-ligand Docking3D Molecular ModelingBinding Pose PredictionMolecular Conformation PredictionMolecular Representation LearningPretrainingProtein-ligand Binding ModelingProtein-ligand Binding Pose PredictionRepresentation Learning For Molecules
Molecular representation learning (MRL) has gained tremendous attention due to its critical role in learning from limited supervised data for applications like drug design. In most MRL methods, molecules are treated as 1D sequential tokens or 2D topology graphs, limiting their ability to incorporate 3D information for downstream tasks and, in particular, making it almost impossible for 3D geometry prediction or generation. Herein, we propose Uni-Mol, a universal MRL framework that significantly enlarges the representation ability and application scope of MRL schemes. Uni-Mol is composed of two models with the same SE(3)-equivariant transformer architecture: a molecular pretraining model trained by 209M molecular conformations; a pocket pretraining model trained by 3M candidate protein pocket data. The two models are used independently for separate tasks, and are combined when used in protein-ligand binding tasks. By properly incorporating 3D information, Uni-Mol outperforms SOTA in 14/15 molecular property prediction tasks. Moreover, Uni-Mol achieves superior performance in 3D spatial tasks, including protein-ligand binding pose prediction, molecular conformation generation, etc. Finally, we show that Uni-Mol can be successfully applied to the tasks with few-shot data like pocket druggability prediction. The model and data will be made publicly available at \url{https://github.com/dptech-corp/Uni-Mol}
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DROPS (Schloss Dagstuhl – Leibniz Center for Informatics) · 2023 · 76.3K citations · Full text
Highly accurate protein structure prediction with AlphaFold
John Jumper, Alexander Pritzel, Tim Green et al. · Nature · 2021 · 45.2K citations · Full text