NMR line shapes and multi-state binding equilibria.

摘要: Biological function of proteins relies on conformational transitions and binding specific ligands. Protein–ligand interactions are thermodynamically kinetically coupled to changes in protein structures as conceptualized by the models pre-existing equilibria induced fit. NMR spectroscopy is particularly sensitive complex ligand-binding modes—NMR line-shape analysis can provide for thermodynamic kinetic constants with site-specific resolution. However, broad use line shape hampered complexity shapes multi-state systems. To facilitate interpretation such spectral patterns, I computationally explored systems where isomerization or dimerization a (receptor) molecule ligand. Through an extensive multiple exchange regimes family three-state models, identified signature features guide experimentalist recognizing interaction mechanisms. Results show that distinct may produce very similar patterns. also discussed aggregation receptor possible source spurious provided suggestions complementary experiments ensure reliable mechanistic insight.