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Ligands

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From mundane to surprising nonadditivity: drivers and impact on ML models.

Journal of computer-aided molecular design
Nonadditivity (NA) in Structure-Activity and Structure-Property Relationship (SAR) data is a rare but very information rich phenomenon. It can indicate conformational flexibility, structural rearrangements, and errors in assay results and structural ...

Transcriptionally Conditional Recurrent Neural Network for De Novo Drug Design.

Journal of chemical information and modeling
Computational molecular generation methods that generate chemical structures from gene expression profiles have been actively developed for de novo drug design. However, most omics-based methods involve complex models consisting of multiple neural ne...

HydraScreen: A Generalizable Structure-Based Deep Learning Approach to Drug Discovery.

Journal of chemical information and modeling
We propose HydraScreen, a deep-learning framework for safe and robust accelerated drug discovery. HydraScreen utilizes a state-of-the-art 3D convolutional neural network designed for the effective representation of molecular structures and interactio...

Binding and sensing diverse small molecules using shape-complementary pseudocycles.

Science (New York, N.Y.)
We describe an approach for designing high-affinity small molecule-binding proteins poised for downstream sensing. We use deep learning-generated pseudocycles with repeating structural units surrounding central binding pockets with widely varying sha...

MDFit: automated molecular simulations workflow enables high throughput assessment of ligands-protein dynamics.

Journal of computer-aided molecular design
Molecular dynamics (MD) simulation is a powerful tool for characterizing ligand-protein conformational dynamics and offers significant advantages over docking and other rigid structure-based computational methods. However, setting up, running, and an...

Future Perspectives of Artificial Intelligence in Bone Marrow Dosimetry and Individualized Radioligand Therapy.

Seminars in nuclear medicine
Radioligand therapy is an emerging and effective treatment option for various types of malignancies, but may be intricately linked to hematological side effects such as anemia, lymphopenia or thrombocytopenia. The safety and efficacy of novel therano...

Machine Learned Classification of Ligand Intrinsic Activities at Human μ-Opioid Receptor.

ACS chemical neuroscience
Opioids are small-molecule agonists of μ-opioid receptor (μOR), while reversal agents such as naloxone are antagonists of μOR. Here, we developed machine learning (ML) models to classify the intrinsic activities of ligands at the human μOR based on t...

Versatile Framework for Drug-Target Interaction Prediction by Considering Domain-Specific Features.

Journal of chemical information and modeling
Predicting drug-target interactions (DTIs) is one of the crucial tasks in drug discovery, but traditional wet-lab experiments are costly and time-consuming. Recently, deep learning has emerged as a promising tool for accelerating DTI prediction due t...

Docking Score ML: Target-Specific Machine Learning Models Improving Docking-Based Virtual Screening in 155 Targets.

Journal of chemical information and modeling
In drug discovery, molecular docking methods face challenges in accurately predicting energy. Scoring functions used in molecular docking often fail to simulate complex protein-ligand interactions fully and accurately leading to biases and inaccuraci...

Proximity Graph Networks: Predicting Ligand Affinity with Message Passing Neural Networks.

Journal of chemical information and modeling
Message passing neural networks (MPNNs) on molecular graphs generate continuous and differentiable encodings of small molecules with state-of-the-art performance on protein-ligand complex scoring tasks. Here, we describe the proximity graph network (...