AIMC Topic: Ligands

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Ligand-receptor interaction profiling as a predictive biomarker for anti-PD-1 therapy response in melanoma.

Clinical and experimental medicine
Cell-to-cell communication through ligand-receptor (LR) interactions can fundamentally shape the tumor microenvironment and immune responses, but the full spectrum of these interactions in anti-PD-1 therapy remains unexplored. We developed a predicti...

μOR-ligand: target-aware view-based hybrid feature selection for μ-opioid receptor ligand functional classification.

Journal of computer-aided molecular design
Understanding active functional class (agonist vs antagonist) at the human μ-opioid receptor (μOR) is critical for drug discovery and safety assessment. While recent machine learning models such as ExtraTrees (ET) and message-passing neural networks ...

Unveiling molecular moieties through hierarchical Grad-CAM graph explainability.

BMC bioinformatics
BACKGROUND: Virtual Screening (VS) has become an essential tool in drug discovery, enabling the rapid and cost-effective identification of potential bioactive molecules. Among recent advancements, Graph Neural Networks (GNNs) have gained prominence f...

Fast and Reliable NMR-Based Fragment Scoring for Drug Discovery.

Journal of the American Chemical Society
Fragment-Based Drug Discovery (FBDD) is a powerful strategy used in the development of new therapeutics. Molecular fragments are screened against a target protein, where interactions are typically characterized by a low affinity. Nuclear Magnetic Res...

A generalizable deep learning framework for structure-based protein-ligand affinity ranking.

Proceedings of the National Academy of Sciences of the United States of America
Rapid and accurate estimation of protein-ligand binding affinities is crucial for early-stage drug discovery, yet hindered by a trade-off between the accuracy of gold-standard physics-based methods and the speed of simpler empirical scoring functions...

TEMPL: A Template-Based Protein-Ligand Pose Prediction Baseline.

Journal of chemical information and modeling
Pose prediction of ligands to proteins remains a central challenge of structure-based drug design. Although data leakage and generalizability concerns remain, data-driven methods for pose prediction (i.e., based on deep learning and diffusion) now ro...

Ligand Dissociation Pathways from Membrane Receptors Revealed by Weighted Ensemble Simulations.

The journal of physical chemistry. B
G-protein-coupled receptors (GPCRs) are pivotal in cellular signal transduction and serve as key drug targets. Among them, the β-adrenergic receptors (βAR and βAR) regulate cardiovascular function and are activated by endogenous catecholamines, norep...

FragOPT: An ML-Driven Computational Workflow for Rational Fragments Optimization Toward Lead Compounds.

Journal of chemical information and modeling
Advances in machine learning (ML) offer significant potential to accelerate drug discovery. Although mathematical modeling and ML have become crucial in predicting drug-target interactions and properties, the complexity of chemical space and the "bla...

On Free Energy Calculations in Drug Discovery.

Accounts of chemical research
ConspectusThis Account discusses recent progress and challenges in binding free energy computations, focusing on two classes of enhanced sampling techniques: alchemical transformations and path-based methods. Binding free energy is a crucial metric i...

More Sophisticated Is Not Always Better: A Comparison of Similarity Measures for Unsupervised Learning of Pathways in Biomolecular Simulations.

The journal of physical chemistry. B
Finding process pathways in molecular simulations such as the unbinding paths of small molecule ligands from their binding sites at protein targets in a set of trajectories via unsupervised learning approaches requires the definition of a suitable si...