DNA: From rigid base-pairs to semiflexible polymers

The sequence-dependent elasticity of double-helical DNA on a nm length scale can be captured by the rigid base-pair model, whose strains are the relative position and orientation of adjacent base-pairs. Corresponding elastic potentials have been obtained from all-atom MD simulation and from high-resolution structural data. On the scale of a hundred nm, DNA is successfully described by a continuous worm-like chain model with homogeneous elastic properties characterized by a set of four elastic constants, which have been directly measured in single-molecule experiments. We present here a theory that links these experiments on different scales, by systematically coarse-graining the rigid base-pair model for random sequence DNA to an effective worm-like chain description. The average helical geometry of the molecule is exactly taken into account in our approach. We find that the available microscopic parameters sets predict qualitatively similar mesoscopic parameters. The thermal bending and twisting persistence lengths computed from MD data are 42 and 48 nm, respectively. The static persistence lengths are generally much higher, in agreement with cyclization experiments. All microscopic parameter sets predict negative twist-stretch coupling. The variability and anisotropy of bending stiffness in short random chains lead to non-Gaussian bend angle distributions, but become unimportant after two helical turns.Comment: 13 pages, 6 figures, 6 table

Strategies for synthesis of yardsticks and abaci for nanometre distance measurements by pulsed EPR

Silvia Valera is grateful for support by EPSRC and Bela E. Bode acknowledges support by EastCHEM.Pulsed electron paramagnetic resonance (EPR) techniques have been found to be an efficient tool for elucidation of structure in complex biological systems as they give access to distances in the nanometre range. These measurements can provide additional structural information such as relative orientations, structural flexibility or aggregation states. A wide variety of model systems for calibration and optimisation of pulsed experiments has been synthesised. Their design is based on mimicking biological systems or materials in specific properties such as the distances themselves and the distance distributions. Here, we review selected approaches to the synthesis of chemical systems bearing two or more spin centres, such as nitroxide or trityl radicals, metal ions or combinations thereof and sketch their application in pulsed EPR distance measurements.Publisher PDFPeer reviewe

Role of Internal Motions and Molecular Geometry on the NMR Relaxation of Hydrocarbons

The role of internal motions and molecular geometry on $^1$H NMR relaxation times $T_{1,2}$ in hydrocarbons is investigated using MD (molecular dynamics) simulations of the autocorrelation functions for in{\it tra}molecular $G_R(t)$ and in{\it ter}molecular $G_T(t)$ $^1$H-$^1$H dipole-dipole interactions arising from rotational ($R$) and translational ($T$) diffusion, respectively. We show that molecules with increased molecular symmetry such as neopentane, benzene, and isooctane show better agreement with traditional hard-sphere models than their corresponding straight-chain $n$-alkane, and furthermore that spherically-symmetric neopentane agrees well with the Stokes-Einstein theory. The influence of internal motions on the dynamics and $T_{1,2}$ relaxation of $n$-alkanes are investigated by simulating rigid $n$-alkanes and comparing with flexible (i.e. non-rigid) $n$-alkanes. Internal motions cause the rotational and translational correlation-times $\tau_{R,T}$ to get significantly shorter and the relaxation times $T_{1,2}$ to get significantly longer, especially for longer-chain $n$-alkanes. Site-by-site simulations of $^1$H's along the chains indicate significant variations in $\tau_{R,T}$ and $T_{1,2}$ across the chain, especially for longer-chain $n$-alkanes. The extent of the stretched (i.e. multi-exponential) decay in the autocorrelation functions $G_{R,T}(t)$ are quantified using inverse Laplace transforms, for both rigid and flexible molecules, and on a site-by-site bases. Comparison of $T_{1,2}$ measurements with the site-by-site simulations indicate that cross-relaxation (partially) averages-out the variations in $\tau_{R,T}$ and $T_{1,2}$ across the chain of long-chain $n$-alkanes. This work also has implications on the role of nano-pore confinement on the NMR relaxation of fluids in the organic-matter pores of kerogen and bitumen

Exploring the flexibility of MIL-47(V)-type materials using force field molecular dynamics simulations

The flexibility of three MIL-47(V)-type materials (MIL-47, COMOC-2, and COMOC-3) has been explored by constructing the pressure versus volume and free energy versus volume profiles at various temperatures ranging from 100 to 400 K This is done with first-principles-based force fields using the recently proposed QuickFF parametrization protocol. Specific terms were added for the materials at hand to describe the asymmetry of the one-dimensional vanadium oxide chain and to account for the flexibility of the organic linkers. The force fields are used in a series of molecular dynamics simulations at fixed volumes but varying unit cell shapes. The three materials show a distinct pressure-volume behavior, which underlines the ability to tune the mechanical properties by varying the linkers toward different applications such as nanosprings, dampers, and shock absorbers

Anharmonic Torsional Stiffness of DNA Revealed under Small External Torques

DNA supercoiling plays an important role in a variety of cellular processes. The torsional stress related with supercoiling may be also involved in gene regulation through the local structure and dynamics of the double helix. To check this possibility steady torsional stress was applied to DNA in the course of all-atom molecular dynamics simulations. It is found that small static untwisting significantly reduces the torsional persistence length ($l_t$) of GC-alternating DNA. For the AT-alternating sequence a smaller effect of the opposite sign is observed. As a result, the measured $l_t$ values are similar under zero stress, but diverge with untwisting. The effect is traced to sequence-specific asymmetry of local torsional fluctuations, and it should be small in long random DNA due to compensation. In contrast, the stiffness of special short sequences can vary significantly, which gives a simple possibility of gene regulation via probabilities of strong fluctuations. These results have important implications for the role of local DNA twisting in complexes with transcription factors.Comment: 8 pages, 5 figures, to appear in Phys. Rev. Let

Rational design and dynamics of self-propelled colloidal bead chains: from rotators to flagella

The quest for designing new self-propelled colloids is fuelled by the demand for simple experimental models to study the collective behaviour of their more complex natural counterparts. Most synthetic self-propelled particles move by converting the input energy into translational motion. In this work we address the question if simple self-propelled spheres can assemble into more complex structures that exhibit rotational motion, possibly coupled with translational motion as in flagella. We exploit a combination of induced dipolar interactions and a bonding step to create permanent linear bead chains, composed of self-propelled Janus spheres, with a well-controlled internal structure. Next, we study how flexibility between individual swimmers in a chain can affect its swimming behaviour. Permanent rigid chains showed only active rotational or spinning motion, whereas longer semi-flexible chains showed both translational and rotational motion resembling flagella like-motion, in the presence of the fuel. Moreover, we are able to reproduce our experimental results using numerical calculations with a minimal model, which includes full hydrodynamic interactions with the fluid. Our method is general and opens a new way to design novel self-propelled colloids with complex swimming behaviours, using different complex starting building blocks in combination with the flexibility between them.Comment: 27 pages, 10 figure