MSITE

MSITE analyzes structural changes in protein complexes to identify neighboring amino acids and map indirect interactions that influence nuclear receptor ligand- and co-activator–dependent transcriptional activity.

Key Features:

• Identification of Neighboring Amino Acids: Automatically identifies and lists nearest-neighbor residues of specified amino acids within protein complexes based on structural coordinates.
• Comparative Structural Analysis: Compares multiple protein complex structures simultaneously, supporting analysis of an arbitrary number of complexes to reveal ligand-dependent structural differences.
• Indirect Interaction Mapping: Detects residues that change conformation distant from direct ligand contacts to map potential indirect interactions between binding-pocket and outer-surface residues relevant to co-activator recruitment.

Scientific Applications:

• Nuclear receptor structural studies: Applied to investigate nuclear receptors such as the vitamin D receptor (VDR), including ligand-specific effects on amino-acid side-chain conformations.
• Ligand-dependent signaling and co-activator recruitment: Supports analysis of how different ligands, including 20-epi-1alpha,25-(OH)2D3, induce subtle conformational changes that propagate through receptor structures and may modulate co-activator interactions and transcriptional activity.

Methodology:

Automatically lists neighboring amino acids from crystallographic structural data and compares neighbor lists across ligand-bound states to infer propagation of conformational changes and potential indirect interactions.