Smoluchowski dynamics of the vnd/NK-2 homeodomain fromDrosophila melanogaster: First-order mode-coupling approximation

Penna, Giovanni La; Mormino, Michele; Pioli, Franco; Perico, Angelo; Fioravanti, R.; Gruschus, James M.; Ferretti, James A.

doi:10.1002/(sici)1097-0282(199903)49:3<235::aid-bip5>3.0.co;2-7

Cited by 13 publications

(4 citation statements)

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“…35 ). This problem can be circumvented by using the so-called "model-free" approach 31,32 that assumes a simple form for the correlation function: (12) where δ a,b is the Kronecker delta, τ loc is the correlation time for local motion, and S is the generalized order parameter:…”

Section: The Local Mobility Modementioning

confidence: 99%

A Model of Interdomain Mobility in a Multidomain Protein

2007

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Domain mobility plays essential role in the biological function of multidomain systems. The characteristic times of domain motions fall into the interval from nano-to milliseconds, amenable to NMR studies. Proper analysis of NMR relaxation data for these systems in solution has to account for interdomain motions, in addition to the overall tumbling and local intradomain dynamics. Here we propose a model of interdomain mobility in a multi-domain protein, which considers domain reorientations as exchange/interconversion between two distinct conformational states of the molecule, combined with fully anisotropic overall tumbling. Analysis of 15 N-relaxation data for Lys48-linked di-ubiquitin at pH4.5 and 6.8 showed that this model adequately fits the experimental data and allows characterization of both structural and motional properties of di-ubiquitin, thus providing information about the relative orientation of ubiquitin domains in both interconverting states. The analysis revealed that the two domains reorient on a time scale of 9-30 ns, with the amplitudes sufficient for allowing a protein ligand access to the binding sites sequestered at the interface in the closed conformation. The analysis of possible mechanism controlling the equilibrium between the interconverting states in di-ubiquitin points toward protonation of His68, which results in three different charged states of the molecule, with zero, +e, and +2e net charge. Only two of the three states are noticeably populated at pH4.5 or 6.8, which assures applicability of the two-state model to di-ubiquitin at these conditions. We also compare our model with the "extended modelfree" approach and discuss possible future developments of the model.

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Section: The Local Mobility Modementioning

confidence: 99%

A Model of Interdomain Mobility in a Multidomain Protein

2007

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“…We have applied the same devices to a 60 residue protein in a known structure, a rigid representation of a segment of vnd/NK-2, the Drosophila melanogaster ventral nervous defective homeodomain protein. 11,2 We have approximated the protein as a chain of 60 beads centered on the CR atoms, each with a hydrodynamic radius computed as the sum of the radii of multiple elementary units, (i.e., CH 2 , CdO, etc.) that in turn are computed within the van der Waals volume increment method.…”

Section: Results For the Rigid 3-d Structure Of A Proteinmentioning

confidence: 99%

“…1 In this framework, the dynamics of stiff synthetic and biological macromolecules, such as proteins and DNA double helices, may be described as the diffusion of fluctuating three-dimensional (3-D) structures. 2 For these systems, the rotational dynamics of 3-D rigid structures represents a natural step and also a major contribution to the local dynamics of the fluctuating chain. 2,3 In this paper we develop simplified methods in the mode-coupling diffusion approach to obtain time correlation functions (TCFs) for local tensor variables of large rigid molecular systems.…”

Section: Introductionmentioning

confidence: 99%

“…2 For these systems, the rotational dynamics of 3-D rigid structures represents a natural step and also a major contribution to the local dynamics of the fluctuating chain. 2,3 In this paper we develop simplified methods in the mode-coupling diffusion approach to obtain time correlation functions (TCFs) for local tensor variables of large rigid molecular systems.…”

Section: Introductionmentioning

confidence: 99%

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Mode-Coupling Smoluchowski Dynamics of Polymers in the Limit of Rigid Structures

1998

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The time correlation functions of molecular configurational variables are calculated using a mode-coupling expansion of the Smoluchowski generalized diffusion equation with hydrodynamic interactions. For fluctuating three-dimensional structures the computation of the dynamics of the rigid limit represents a fundamental first step in the mode-coupling approach. For large rigid systems, using the three first-order vector modes of a noninfinite rate, higher order basis sets of the proper tensor rank are built to give the required mode-coupling dynamics. The results are found to be in very good agreement with the exact results obtained by an analytical solution of the rotational diffusion equation of rigid bodies. These rigid limits give simple accurate basis sets in the maximum correlation approximation (MCA) to the mode-coupling diffusion dynamics of fluctuating stiff synthetic polymers and biopolymers such as proteins and DNA double helices.

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