Two-Dimensional NMR Lineshape Analysis.
NMR titration experiments are a rich source of structural, mechanistic, thermodynamic and kinetic information on biomolecular interactions, which can be extracted through the quantitative analysis of resonance lineshapes. However, applications of such analyses are frequently limited by peak overlap inherent to complex biomolecular systems. Moreover, systematic errors may arise due to the analysis of two-dimensional data using theoretical frameworks developed for one-dimensional experiments. Here we introduce a more accurate and convenient method for the analysis of such data, based on the direct quantum mechanical simulation and fitting of entire two-dimensional experiments, which we implement in a new software tool, TITAN (TITration ANalysis). We expect the approach, which we demonstrate for a variety of protein-protein and protein-ligand interactions, to be particularly useful in providing information on multi-step or multi-component interactions.
Institute of Structural and Molecular Biology, University College London and Birkbeck College, London WC1E 6BT, UK.
Christopher A
CA
Waudby
Institute of Structural and Molecular Biology, University College London and Birkbeck College, London WC1E 6BT, UK.
Andres
A
Ramos
Institute of Structural and Molecular Biology, University College London and Birkbeck College, London WC1E 6BT, UK.
Lisa D
LD
Cabrita
Institute of Structural and Molecular Biology, University College London and Birkbeck College, London WC1E 6BT, UK.
John
J
Christodoulou
D019295:Computational Biology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D046912:Multiprotein Complexes / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D012984:Software
D008024:Ligands; D046912:Multiprotein Complexes; D011506:Proteins