Dynamics of Protein-Ligand Interactions
| Název česky | Dynamika interakcí protein-ligand |
|---|---|
| Autoři | |
| Rok publikování | 2006 |
| Druh | Článek ve sborníku |
| Konference | Frontieres of Biomolecular NMR |
| Fakulta / Pracoviště MU | |
| Citace | |
| Obor | Biochemie |
| Klíčová slova | NMR; proteins; dynamics; molecular dynamics; NMR relaxation |
| Popis | Binding of mouse pheromones to major urinary proteins (MUPs) represents a typical example of interactions between lipocalins and their small hydrophobic ligands. Previously, based on the model-free analysis of 15N relaxation data, we observed that the backbone flexibility of MUP-I increased slightly upon pheromone binding, in contrast to the decreased flexibility expected for induced-fit interactions. To shed the light on this unusual observation, we have performed an independent study adopting different methodology. Backbone dynamics of mouse major urinary protein I (MUP-I) was studied by 15N NMR relaxation at multiple temperatures for a complex of MUP-I with its natural pheromonal ligand, 2-sec-4,5-dihydrothiazole, and for the free protein. Graphical analysis of the reduced spectral density values provided an unbiased qualitative picture of the internal motions. Quantitative parameters were obtained using a novel method of simultaneous data fitting at multiple temperatures to several models of different complexity. The relaxation data were complemented by the molecular dynamics simulations. Correlation functions and frequency-dependent order parameters were calculated from the simulated motions of the amide NH vectors. Comparison of the experimental and simulated order parameters and the information about slow conformational exchanges provided a picture of the molecular motions and offered a structural explanation for the observed difference in the dynamics of the free and bound MUP-I. |
| Související projekty: |