LARMD

LARMD profiles ligand-driven protein dynamics to analyze activation mechanisms, ligand selectivity (including ERβ/ERα determinants), and structural factors that inform drug design and site-directed mutagenesis.

Key Features:

• Integration of resources: Integrates multiple bioinformatic resources into a cohesive computational protocol for analyzing ligand–receptor systems.
• Protein dynamics profiling: Profiles ligand-driven protein dynamics to investigate activation mechanisms and ligand-induced conformational changes.
• Selectivity determinant identification: Identifies residues Ile373/Met421 and Met336/Leu384 as determinants of ERβ/ERα selectivity and highlights Met336 for ERβ specificity.
• Structural element analysis: Analyzes the effects of helix H8, helix H11, and the H7-H8 loop on the migration of selective agonists such as WAY-244.
• Visualization of dynamics: Produces visualizations of ligand-driven protein dynamics to support interpretation of conformational changes.
• Support for design and mutagenesis: Provides computational evidence to guide design of new ligands and site-directed mutagenesis strategies.

Scientific Applications:

• Estrogen receptor activation profiling: Profiling activation mechanisms of estrogen receptors with a focus on ERβ-selective pathways relevant to inflammatory disease and cancers.
• Drug discovery: Informing design of selective agonists and ligands by identifying selectivity determinants and migration pathways.
• Mechanistic studies: Studying ligand-induced conformational changes relevant to signal transduction, cellular regulation, and catalysis.

Methodology:

Integration of multiple bioinformatic resources into a cohesive computational protocol and computational analyses to profile ligand-driven protein dynamics and identify selectivity-determining residues and structural contributors.