GPCR-ModSim

GPCR-ModSim performs structural modeling and molecular dynamics equilibration of G-protein coupled receptors (GPCRs) to generate and refine 3D receptor models from amino acid sequences for structural and pharmacological studies.

Key Features:

• Homology modeling: Generates 3D molecular models from amino acid sequences using updated structural templates.
• Multiple-template homology modeling: Supports combining multiple templates to build receptor models.
• Conformational coverage: Accommodates inactive, partially-active, and active receptor states via updated templates.
• Membrane insertion: Inserts receptor models into a membrane environment prior to refinement.
• Molecular dynamics (MD) equilibration: Performs MD equilibration to refine generated or uploaded GPCR structures.
• Restraints from conserved contacts: Incorporates distance restraints derived from a conserved network of helical contacts during equilibration.
• Non-protein elements: Allows inclusion of orthosteric and allosteric ligands, structural waters, and ions in models.
• Validation: Methodology and results validated through participation in GPCR Dock 2013.

Scientific Applications:

• Structural biology: Construction and refinement of GPCR 3D models for interpretation of structure-function relationships.
• Pharmacology: Modeling of receptor states and inclusion of orthosteric/allosteric ligands to study ligand–receptor interactions.
• Drug discovery: Provision of refined receptor models to support structure-based drug design and related studies.
• Conformational dynamics: Exploration of dynamic conformations and conformational transitions of GPCRs via MD equilibration.

Methodology:

Uses homology-modeling techniques including multiple-template homology modeling and updated templates to generate 3D models from amino acid sequences, performs membrane insertion and molecular dynamics (MD) equilibration (applying distance restraints derived from a conserved network of helical contacts), and supports inclusion of orthosteric/allosteric ligands, structural waters, and ions to refine generated or uploaded GPCR structures.