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bioRxiv · 10.1101/2020.12.11.421768

Target2DeNovoDrug : a novel programmatic tool for deep learning based de novo drug design for a target of interest

Madaj, R.·Geoffrey A S, B.·Valluri, P. P.·Sanker, A.
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Abstract

The past decade has seen a surge in the range of application data science, machine learning, deep learning, and AI methods to drug discovery. The presented work involves an assemblage of a variety of AI methods for drug discovery along with the incorporation of in silico techniques to provide a holistic tool for automated drug discovery. When drug candidates are required to be identified for a particular drug target of interest, the user is required to provide the tool target signatures in the form of an amino acid sequence or its corresponding nucleotide sequence. The tool collects data registered on PubChem required to perform an automated QSAR and with the validated QSAR model, prediction and drug lead generation are carried out. This protocol we call Target2Drug. This is followed by a protocol we call Target2DeNovoDrug wherein novel molecules with likely activity against the target are generated de novo using a generative LSTM model. It is often required in drug discovery that the generated molecules possess certain properties like drug-likeness, and therefore to optimize the generated de novo molecules toward the required drug-like property we use a deep learning model called DeepFMPO, and this protocol we call Target2DeNovoDrugPropMax. This is followed by the fast automated AutoDock-Vina based in silico modeling and profiling of the interaction of optimized drug leads and the drug target. This is followed by an automated execution of the Molecular Dynamics protocol that is also carried out for the complex identified with the best protein-ligand interaction from the AutoDock-Vina based virtual screening. The results are stored in the working folder of the user. The code is maintained, supported, and provide for use in the following GitHub repository https://github.com/bengeof/Target2DeNovoDrugPropMax

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Madaj, R., Geoffrey A S, B., Valluri, P. P., Sanker, A.. 2020-12-11. Target2DeNovoDrug : a novel programmatic tool for deep learning based de novo drug design for a target of interest. https://doi.org/10.1101/2020.12.11.421768

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