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Abstract A machine learning-based drug screening technique has been developed and optimized using convolutional neural network-derived fingerprints. The optimization of weights in the neural network-based fingerprinting technique was compared with fixed Morgan fingerprints in regard to binary classification on drug-target binding affinity. The assessment was carried out using six different target proteins using randomly chosen small molecules from the ZINC15 database for training. This new architecture proved to be more efficient in screening molecules that less favorably bind to specific targets and retaining molecules that favorably bind to it. Scientific contribution We have developed a new neural fingerprint-based screening model that has a significant ability to capture hits. Despite using a smaller dataset, this model is capable of mapping chemical space similar to other contemporary algorithms designed for molecular screening. The novelty of the present algorithm lies in the speed with which the models are trained and tuned before testing its predictive capabilities and hence is a significant step forward in the field of machine learning-embedded computational drug discovery.
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Energy-based generative models for target-specific drug discovery
Drug targets are the main focus of drug discovery due to their key role in disease pathogenesis. Computational approaches are widely applied to drug development because of the increasing availability of biological molecular datasets. Popular generative approaches can create new drug molecules by learning the given molecule distributions. However, these approaches are mostly not for target-specific drug discovery. We developed an energy-based probabilistic model for computational target-specific drug discovery. Results show that our proposed TagMol can generate molecules with similar binding affinity scores asrealmolecules. GAT-based models showed faster and better learning relative to Graph Convolutional Network baseline models.
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- PAR ID:
- 10539715
- Publisher / Repository:
- Frontiers
- Date Published:
- Journal Name:
- Frontiers in Molecular Medicine
- Volume:
- 3
- ISSN:
- 2674-0095
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fmmed.2023.1160877
