Protein–Ligand Interactions: Structural and Dynamic Insights for Drug Discovery

Protein–ligand interactions are central to molecular recognition and to the regulation of biological function. They also provide a mechanistic foundation for drug discovery and repurposing. Advances in X-ray crystallography, cryo-electron microscopy, nuclear magnetic resonance spectroscopy, molecular dynamics, and integrative structural biology now make it possible to examine protein–ligand complexes across multiple conformational and functional states. These approaches are revealing how binding affinity, specificity, kinetics, allostery, and conformational dynamics shape protein function in health and disease.Important challenges remain. Transient and weak interactions can be difficult to capture, binding energetics are not always well resolved, and computational predictions still require careful experimental validation. Connecting atomic-level binding mechanisms with pathogenic mutations, protein dysfunction, disease progression, and therapeutic response also requires closer integration between structural biophysics, computational chemistry, pharmacology, and disease biology.This Research Topic aims to advance the mechanistic understanding of protein–ligand recognition and its implications for drug discovery and repurposing. We welcome studies that connect structural or biophysical evidence to binding thermodynamics, kinetics, conformational change, allosteric regulation, molecular mechanism, or pharmacological function. Experimental, computational, and hybrid approaches are encouraged when they provide a clear structural or biophysical interpretation of ligand binding. AI-assisted structure prediction, molecular simulation, and data-driven methods are welcome as enabling tools, particularly when combined with experimental validation or mechanistic analysis.The collection is intended for research at the interface of protein structure, dynamics, molecular recognition, and therapeutic design. Studies focused solely on high-throughput virtual screening, generic docking benchmarks, or drug discovery without a clear connection to protein structure, ligand-binding mechanism, or biophysical evidence are outside the primary scope.To gather further insights into this field, we welcome contributions addressing, but not limited to, the following themes:— Atomic and molecular mechanisms governing protein–ligand recognition, affinity, specificity, and selectivity— Structural and biophysical characterization of protein–drug, protein–metabolite, and protein–cofactor complexes using crystallography, cryo-EM, NMR, or integrative methods— Binding thermodynamics, kinetics, transient interactions, conformational ensembles, induced fit, and conformational selection— Allosteric modulation and long-range communication between ligand-binding sites and functional regions— Structural effects of pathogenic mutations, misfolding, disorder, and disease-associated protein dysfunction— Molecular dynamics simulations, free-energy calculations, docking, and multiscale methods for explaining ligand binding and affinity— AI-assisted structure prediction and data-driven identification of binding sites, allosteric pockets, and repurposing opportunities— Structure-guided drug discovery and repurposing supported by high-resolution structural, biophysical, or pharmacological evidence— Integrative experimental–computational frameworks connecting molecular structure, binding mechanism, kinetics, and biological or therapeutic outcomes. Topic editors: Belen Otero Carrasco, Paloma Tejera Nevado, Jannette Carey Source: https://www.frontiersin.org/research-topics/83187/protein-ligand-interactions-structural-and-dynamic-insights-for-drug-discovery