Molecular dynamics study of major urinary protein-pheromone interactions: A structural model for ligand-induced flexibility increase

Pavel Macek¹, Petr Novák¹, Lukáš Žídek¹ and Vladimír Sklenář¹

¹National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5/A4, Brno, 611 37, Czech Republic

Recently, two independent ¹⁵N NMR relaxation studies [1,2] indicated that in contrast to the decreased flexibility expected for induced-fit interactions, the backbone flexibility of major urinary protein isoform I (MUP-I) slightly increased upon complex formation with its natural pheromone 2-sec-butyl-4,5-dihydrothiazol. We have analyzed motions in terms of frequency-dependent and conformation-dependent order parameters S² by molecular dynamics simulations of free- and complexed protein. In general, calculated order parameters S² agree with the NMR relaxation data. Structural analysis supplied evidence that mobility in different regions can be attributed to small conformational changes of free- and complexed protein, which results from hydrogen bonding network modifications [3].

1. L.Žídek, M.J.Stone, S.M.Lato, M.D.Pagel, Z.S.Miao, A.D.Ellington and M.V.Novotny, Biochemistry, 38, (1999), 9850.

2. H.Křížová, L.Žídek, M.J.Stone, M.V.Novotny and V.Sklenář, J.Biomol.NMR, 28, (2004), 369.

3. P.Macek, P.Novák, H.Křížová, L.Žídek, V.Sklenář, FEBS letters, In Press.