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LS-MolGen: Ligand-and-Structure Dual-driven Deep Reinforcement Learning for Target-specific Molecular Generation Improves Binding Affinity and Novelty (preprint)
researchsquare; 2023.
Preprint
in English
| PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2793302.v1
ABSTRACT
Molecule generative models based on deep learning have attracted significant attention in de novo drug design. However, most current generative approaches are either only ligand-based or only structure-based, which do not leverage the complementary knowledge from ligands and the structure of binding target. In this work, we proposed a new ligand and structure combined molecular generative model, LS-MolGen, that integrates representation learning, transfer learning, and reinforcement learning. Focus knowledge from transfer learning and special explore strategy in reinforcement learning enables LS-MolGen to generate novel and active molecules efficiently. The results of evaluation using EGFR and case study of inhibitor design for SARS-CoV-2 Mpro showed that LS-MolGen outperformed other state-of-the-art ligand-based or structure-based generative models and was capable of de novo designing promising compounds with novel scaffold and high binding affinity. Thus, we recommend that this proof-of-concept ligand-and-structure-based generative model will provide a promising new tool for target-specific molecular generation and drug design.
Full text:
Available
Collection:
Preprints
Database:
PREPRINT-RESEARCHSQUARE
Language:
English
Year:
2023
Document Type:
Preprint
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