PT  - JOURNAL ARTICLE
AU  - Christopher Andrew Waudby
AU  - Andres Ramos
AU  - Lisa D. Cabrita
AU  - John Christodoulou
TI  - Two-Dimensional NMR Lineshape Analysis
AID  - 10.1101/039735
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 039735
4099  - http://biorxiv.org/content/early/2016/02/15/039735.short
4100  - http://biorxiv.org/content/early/2016/02/15/039735.full
AB  - 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.