Several different models of the linker histone (LH)–nucleosome complex have been proposed, but none of them has unambiguously revealed the position and binding sites of the LH on the nucleosome. Using Brownian dynamics-based docking together with normal mode analysis of the nucleosome to account for the flexibility of two flanking 10 bp long linker DNAs (L-DNA), we identified binding modes of the H5-LH globular domain (GH5) to the nucleosome. For a wide range of nucleosomal conformations with the L-DNA ends less than 65 Å apart, one dominant binding mode was identified for GH5 and found to be consistent with fluorescence recovery after photobleaching (FRAP) experiments. GH5 binds asymmetrically with respect to the nucleosomal dyad axis, fitting between the nucleosomal DNA and one of the L-DNAs. For greater distances between L-DNA ends, docking of GH5 to the L-DNA that is more restrained and less open becomes favored. These results suggest a selection mechanism by which GH5 preferentially binds one of the L-DNAs and thereby affects DNA dynamics and accessibility and contributes to formation of a particular chromatin fiber structure. The two binding modes identified would, respectively, favor a tight zigzag chromatin structure or a loose solenoid chromatin fiber.
Linker histones are essential for DNA compaction in chromatin. They bind to nucleosomes in a 1:1 ratio forming chromatosomes. Alternative configurations have been proposed in which the globular domain of the linker histone H5 (gH5) is positioned either on- or off-dyad between the nucleosomal and linker DNAs. However, the dynamic pathways of chromatosome assembly remain elusive. Here, we studied the conformational plasticity of gH5 in unbound and off-dyad nucleosome-bound forms with classical and accelerated molecular dynamics simulations. We find that the unbound gH5 converts between open and closed conformations, preferring the closed form. However, the open gH5 contributes to a more rigid chromatosome and restricts the motion of the nearby linker DNA through hydrophobic interactions with thymidines. Moreover, the closed gH5 opens and reorients in accelerated simulations of the chromatosome. Brownian dynamics simulations of chromatosome assembly, accounting for a range of amplitudes of nucleosome opening and different nucleosome DNA sequences, support the existence of both on- and off-dyad binding modes of gH5 and reveal alternative, sequence and conformation-dependent chromatosome configurations. Taken together, these findings suggest that the conformational dynamics of linker histones and nucleosomes facilitate alternative chromatosome configurations through an interplay between induced fit and conformational selection.
The Boltzmann equation for excess Cooper pairs above Tc is derived in the framework of the timedependent Ginzburg-Landau (TDGL) theory using Langevin's approach of the stochastic differential equation. The Newton dynamic equation for the momentum-dependent drift velocity is obtained and the effective drag force is determined by the energy dependent life time of the metastable Cooper pairs. The Newton equation gives just the Drude mobility for the fixed momentum of Cooper pairs. It is shown that the comparison with the well-known result for Aslamazov-Larkin paraconductivity and BCS treatment of the excess Hall effect can give the final determination of all the coefficients of TDGL theory. As a result the intuitive arguments used for an interpretation of the experimental data for fluctuation kinetics are successively introduced. The presented simple picture of the degenerated Bose gas in τ -approximation near the Bose-Einstein condensation temperature can be used for analysis of fluctuation conductivity for the cases of high frequency and external magnetic field for layered and bulk superconductors. The work of the Boltzmann equation is illustrated by frequencydependent Aslamazov-Larkin conductivity in nanowires, in the two-dimensional case and in the case of strong electric field where the TDGL equation is solved directly. There are also derived explicit formulas for the current in the case of arbitrary time dependence of electric field up to THz range, the distribution of fluctuation Cooper pairs for nonparabolic dispersion, the influence of the energy cut-off and the self-consistent equation for the reduced temperature. The general theory is illustrated by formulas for fluctuation conductivity in nanowires and nanostructured superconductors.
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