Smoluchowski dynamics of the vnd/NK-2 homeodomain from Drosophila melanogaster: Second-order maximum correlation approximation

Abstract

The mode coupling diffusion theory is applied to the derivation of local dynamics in proteins in solution. The rotational dynamics of the bonds along the protein sequence are calculated and compared to the experimentally measured nmr 15N spin-lattice relaxation time T1, at 36.5, 60.8, and 81.1 MHz of the vnd/NK-2 homeodomain from Drosophila melanogaster. The starting point for the calculations is the experimental three-dimensional solution structure of the homeodomain determined by multidimensional nmr spectroscopy. The higher order mode-coupling computations are compared also with the recently published first-order approximation calculations. The more accurate calculations improve substantially the first-order ORZLD calculations and show that the role of the strength of the hydrodynamic interactions becomes crucial to fix the order of magnitude of the rotational dynanics for these very compact molecules characterized by partial screening of the internal atoms to water. However, the relative mobility of the bonds along the sequence and the differential fluctuations depend only weakly on the hydrodynamic strength but strongly on the geometry of the three-dimensional structure and on the statistics incorporated into the theory. Both rigid and fluctuating dynamic models are examined, with fluctuations evaluated using molecular dynamics simulations. The comparison with nmr data shows that mode coupling diffusion accounts for the T1 relaxation pattern at low frequency where the rotational tumbling dominates. An important contribution of internal motions in the nanosecond time scale is seen at high frequencies and is discussed in terms of diffusive concepts. (C) 2000 John Wiley and Sons, Inc.