Dynamics of Protein-Ligand Interactions

SKLENÁŘ, Vladimír. Dynamics of Protein-Ligand Interactions. In Frontieres of Biomolecular NMR. Lubjlana: Narodna i univerzitetna knjižnica, Ljubljana, 2006, s. 41-41. ISBN 961-6104-08-X.

Základní údaje

• Originální název: Dynamics of Protein-Ligand Interactions
• Název česky: Dynamika interakcí protein-ligand
• Autoři: SKLENÁŘ, Vladimír (203 Česká republika, garant).
• Vydání: Lubjlana, Frontieres of Biomolecular NMR, od s. 41-41, 1 s. 2006.
• Nakladatel: Narodna i univerzitetna knjižnica, Ljubljana

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Stať ve sborníku
• Obor: 10600 1.6 Biological sciences
• Stát vydavatele: Slovinsko
• Utajení: není předmětem státního či obchodního tajemství
• Kód RIV: RIV/00216224:14310/06:00018241
• Organizační jednotka: Přírodovědecká fakulta
• ISBN: 961-6104-08-X
• Klíčová slova anglicky: NMR; proteins; dynamics; molecular dynamics; NMR relaxation
• Štítky: dynamics, molecular dynamics, NMR, NMR relaxation, proteins
• Příznaky: Mezinárodní význam

Anotace

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.

Anotace česky

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.

Návaznosti

• LC06030, projekt VaV: Název: Biomolekulární centrum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Biomolekulární centrum

• MSM0021622413, záměr: Název: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Proteiny v metabolismu a při interakci organismů s prostředím