A Full-Spectrum Generative Lead Discovery (FSGLD) Pipeline via DRUG-GAN: A Multiscale Method for Drug-like/Target-specific Compound Library Generation.
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Abstract | We present the Full-Spectrum Generative Lead Discovery (FSGLD), a deep learning-driven pipeline for efficient drug lead identification. FSGLD integrates generative modeling with molecular docking, molecular dynamics simulations, ligand-residue interaction profile, MM-PBSA, thermodynamic integration (TI), and experimental validation to bridge theoretical design and practical application. The core multiscale DRUG-GAN models enable design for both drug-like and target-specific compounds across three scenarios: I. generation of random drug-like compounds, II. generation of target-specific compounds, III. generation of target-biased compound series featuring shared chemical structures. FSGLD significantly outperformed traditional computer-aided drug design methods in generating novel chemicals which specifically target the CB2 receptor. Additionally, a computational protocol for TI calculations was established to reduce computation time by 80-90% while maintaining accuracy. By integrating generative models with and evaluation techniques, FSGLD reduces the cost of identifying novel yet viable lead compounds, offering remarkable benefits to both academic and industry. |
Year of Publication | 2025
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Journal | Research square
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Date Published | 05/2025
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ISSN | 2693-5015
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DOI | 10.21203/rs.3.rs-6516504/v1
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PubMed ID | 40470212
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