Effective charge and free energy of DNA inside an ion channel

Translocation of a single stranded DNA (ssDNA) through an alpha-hemolysin channel in a lipid membrane driven by applied transmembrane voltage V was extensively studied recently. While the bare charge of the ssDNA piece inside the channel is approximately 12 (in units of electron charge) measurements of different effective charges resulted in values between one and two. We explain these challenging observations by a large self-energy of a charge in the narrow water filled gap between ssDNA and channel walls, related to large difference between dielectric constants of water and lipid, and calculate effective charges of ssDNA. We start from the most fundamental stall charge $q_s$, which determines the force $F_s= q_s V/L$ stalling DNA against the voltage V (L is the length of the channel). We show that the stall charge $q_s$ is proportional to the ion current blocked by DNA, which is small due to the self-energy barrier. Large voltage V reduces the capture barrier which DNA molecule should overcome in order to enter the channel by $|q_c|V$, where $q_c$ is the effective capture charge. We expressed it through the stall charge $q_s$. We also relate the stall charge $q_s$ to two other effective charges measured for ssDNA with a hairpin in the back end: the charge $q_u$ responsible for reduction of the barrier for unzipping of the hairpin and the charge $q_e$ responsible for DNA escape in the direction of hairpin against the voltage. At small V we explain reduction of the capture barrier with the salt concentration.Comment: Typos are correcte

Dynamics of a bubble formed in double stranded DNA

We study the fluctuational dynamics of a tagged base-pair in double stranded DNA. We calculate the drift force which acts on the tagged base-pair using a potential model that describes interactions at base pairs level and use it to construct a Fokker-Planck equation.The calculated displacement autocorrelation function is found to be in very good agreement with the experimental result of Altan-Bonnet {\it et. al.} Phys. Rev. Lett. {\bf 90}, 138101 (2003) over the entire time range of measurement. We calculate the most probable displacements which predominately contribute to the autocorrelation function and the half-time history of these displacements.Comment: 11 pages, 4 figures. submitted to Phys. Rev. Let

DNA nanotweezers studied with a coarse-grained model of DNA

We introduce a coarse-grained rigid nucleotide model of DNA that reproduces the basic thermodynamics of short strands: duplex hybridization, single-stranded stacking and hairpin formation, and also captures the essential structural properties of DNA: the helical pitch, persistence length and torsional stiffness of double-stranded molecules, as well as the comparative flexibility of unstacked single strands. We apply the model to calculate the detailed free-energy landscape of one full cycle of DNA 'tweezers', a simple machine driven by hybridization and strand displacement.Comment: 4 pages, 5 figure

Interaction of Tet Repressor with Operator DNA and with Tetracycline Studied by Infrared and Raman Spectroscopy

AbstractTet repressor (TetR) is involved in the most abundant mechanism of tetracycline (Tc) resistance of Gram-negative bacteria. Raman spectra were measured for the class D TetR protein, for an oligodeoxyribonucleotide with sequence corresponding to operator site O1, and for the TetR:oligonucleotide complex. TetR forms a complex with [Ni-Tc]+, which does not bind to operator DNA. Raman and infrared measurements indicate nearly identical conformations of TetR with and without [Ni-Tc]+. Differences between the experimental spectrum of the TetR:operator DNA complex and the computed sum of the component spectra provide direct spectroscopic evidence for changes in DNA backbone torsions and base stacking, rearrangement of protein backbone, and specific contacts between TetR residues and DNA bases. Complex formation is connected with intensity decrease at 1376cm−1 (participation of thymine methyl groups), intensity increase at 1467cm−1 (hydrogen bond formation at guanine N7), decreased intensity ratio I854/I823 (increased hydrophobicity of tyrosine environment), increased intensity at 1363cm−1 (increased hydrophobicity of tryptophan ring environment), differences in the range 670–833cm−1 (changes in B-DNA backbone torsions and base stacking), and decreased intensity of the amide I band (structural rearrangement of TetR backbone consistent with a reduction of the distance between the two binding helices)

Molecular Modeling of Nucleic Acid Structure: Energy and Sampling

An overview of computer simulation techniques as applied to nucleic acid systems is presented. This unit expands an accompanying overview unit (UNIT ) by discussing methods used to treat the energy and sample representative configurations. Emphasis is placed on molecular mechanics and empirical force fields.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143698/1/cpnc0708.pd

Empirical corrections to the Amber RNA force field with Target Metadynamics

The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the \u3b1 and \u3b6 backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement

Effect of shear force on the separation of double stranded DNA

Using the Langevin Dynamics simulation, we have studied the effects of the shear force on the rupture of short double stranded DNA at different temperatures. We show that the rupture force increases linearly with the chain length and approaches to the asymptotic value in accordance with the experiment. The qualitative nature of these curves almost remains same for different temperatures but with a shift in the force. We observe three different regimes in the extension of covalent bonds (back bone) under the shear force.Comment: 4 pages, 4 figure

Thermomechanics of DNA

A theory for thermomechanical behavior of homogeneous DNA at thermal equilibrium predicts critical temperatures for denaturation under torque and stretch, phase diagrams for stable B--DNA, supercoiling, optimally stable torque, and the overstretching transition as force-induced DNA melting. Agreement with available single molecule manipulation experiments is excellent.Comment: 4 pages, 5 figures. Lette