Dynamics of major urinary protein-pheromone interactions: Insight by NMR and MD simulations
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Proceedings |
| Conference | ISMAR 2007, Program and Abstracts |
| MU Faculty or unit | |
| Citation | |
| Web | http://ismar2007.sinica.edu.tw/welcome.php |
| Field | Biophysics |
| Keywords | NMR; relaxation; protein-ligand interactions; internal dynamics; N-15; MD simulations; |
| Description | 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 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. |
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