Analysis of electron-transfer rate constant in condensed media with inclusion of inelastic tunneling and nuclear quantum effects.

We have developed a theoretical formulation for evaluating the nonadiabatic electron-transfer (ET) rate constant in condensed medium which takes into account both inelastic electron tunneling and nuclear quantum effects. The derived formula allows us to calculate the ET rate as a function of the free-energy gap between the ET donor and acceptor states using the information on the spectral density associated with environmental polarization fluctuation and the temporal correlation function of electronic tunneling matrix element. Model calculations have been performed illustratively.

DNA duplex length and salt concentration dependence of enthalpy-entropy compensation parameters for DNA melting.

Systematical differential calorimetry experiments on DNA oligomers with different lengths and placed in water solutions with various added salt concentrations may, in principle, unravel important information about the structure and dynamics of the DNA and their water-counterion surrounding. With this in mind, to reinterpret the most recent results of calorimetric experiments on DNA oligomers of such a kind, the recent enthalpy-entropy compensation theory has been used. It is demonstrated that the application of the latter could enable direct estimation of thermodynamic parameters of the microphase transitions connected to the changes in DNA dynamical regimes versus the length of the biopolymers and the ionic strengths of their water solutions, and this calls for much more systematical experimental and theoretical studies in this field.

Conformation dependence of DNA exciton parentage.

Singlet electronic excitations of DNA duplex trimers and tetramers with regular homogeneous base-pair sequences ((dA)n.(dT)n and (dG)n.(dC)n, with n=3, 4) have been investigated in vacuo using semiempirical quantum chemistry in a Zerner's Intermediate Neglect of Differential Overlap (ZINDO) approximation. Frequencies, oscillator strengths, and single-electron assignments of many-electron transitions have been calculated as functions of all 12 possible conformational modes of DNA duplexes. Specific DNA conformational modes responsible for significant changes in the exciton parentage (onset or arrest of the charge-transfer excitons' involvement into observable electronic transition spectra) are revealed. These computational results are thoroughly discussed in connection with numerous data of the most recent relevant experiments.

Physical rationale behind the nonlinear enthalpy-entropy compensation in DNA duplex stability.

The physical-chemical sense of nonlinear entropy-enthalpy compensation based upon the standard thermodynamical parameters of high-temperature melting for doublet units in DNA duplexes has been considered. We are able to show that there are three, with no other constraints equally plausible, principal levels of DNA melting/hybridization description. First, DNA structure assembly/disassembly can be seen from the viewpoint of the conventional equilibrium thermodynamics without taking special care of the heat capacity DeltaC(p) value (by simply setting it equal to zero). Second, it is possible to assume that the DeltaC(p) is finite, but independent of temperature. At this approximation level the high-temperature DNA melting cannot be described, but only some special transition between metastable states of DNA duplexes in water solutions in the vicinity of ice melting point. Third, both the latter transition and the high-temperature DNA melting can be reproduced by one and the same approach, if the DeltaC(p) is assumed to be temperature dependent. These three approximation levels are equally justified from the nonlinear entropy-enthalpy compensation standpoint and by a generalized theory of temperature effects on themodynamical stability as is outlined here. Applicability of each of the approximation levels involved is discussed.

Mutation effects on structural stability of polyglutamine peptides by molecular dynamics simulation.

Huntington's disease patients commonly have glutamine (Q) repeats longer than 37 residues in the Huntingtin protein. This unusual protein will misfold and aggregate to form insoluble amyloid-like fibrils. Although the determination of polyQ structure is very important for elucidation of the aggregation mechanism, this has not yet been accomplished due to the experimental difficulties. In this study, we performed in silico mutation analysis to examine the stability of polyQ peptide on the basis of the beta-helix structure which is known as a possible model. From the results of molecular dynamics simulations for 10ns, some mutant models were found to be unstable, and their stabilities were largely dependent on the position of replaced residues. Besides, to examine the relationship between the aggregation mechanism of polyQ and the stability of the corresponding monomer, we constructed trimer models. Through the trimer studies, we confirmed that the stability of the monomer contributes significantly to that of the oligomer, and found that some mutant polyQs have the ability to inhibit polyQ aggregation. Furthermore, we estimated the free energies in solution and the conformational entropic contributions with normal mode analysis. The entropic contributions were not exhibiting remarkable differences between the models under study compared to the differences in the free energies in solution. Supposing that the stability of monomer is associated with aggregation process, the beta-helix structure has been found to be somewhat inconsistent with the experimental results in this study. Our results thus indicate the necessity for the revalidation of the beta-helix model.

Conformational dependence of DNA ballistic conductivity.

With the atomistic Kubo-Verges method we calculate the ballistic conductance of various conformers of DNA (A,B,Z), as well as intermediate and composite conformations, using experimental structures and model complexes. For duplexes with 6 and 15 base pairs, we find that the valence band conductivity near the Fermi edge varies dramatically between the different conformations, most notably for the B-to-Z transition. The latter conductivity differences are largely unchanged both in the presence and in the absence of trimethylthiol linkers between DNA and gold electrodes in vacuo, but become much less drastic when explicit molecular dynamics and water-counterion surrounding of B- and Z-DNA are taken into account. Based on atomistic structural models, we argue that changes in the electrostatic energy in the presence of an applied external electric field can induce conformational switching that may be exploited in novel DNA-based memory devices of high packing density.

Molecular dynamics simulation study on the structural stabilities of polyglutamine peptides.

It is known that Huntington's disease patients commonly have glutamine (Q) repeat sequences longer than a critical length in the coding area of Huntingtin protein in their genes. As the polyglutamine (polyQ) region becomes longer than the critical length, the disease occurs and Huntingtin protein aggregates, both in vitro and in vivo, as suggested by experimental and clinical data. The determination of polyglutamine structure is thus very important for elucidation of the aggregation and disease mechanisms. Here, we perform molecular dynamics calculations on the stability of the structure based on the beta-helix structure suggested by Perutz et al. (2002) [Perutz, M.F., Finch, J.T., Berriman, J., Lesk, A., 2002. Amyloid fibers are water-filled nanotubes. Proc. Natl. Acad. Sci. USA 99, 5591]. We ensure that perfect hydrogen bonds are present between main chains of the beta-helix based on the previous studies, and perform simulations of stretches with 20, 25, 30, 37 and 40 glutamine residues (20Q, 25Q, 30Q, 37Q and 40Q) for the Perutz models with 18.5 and 20 residues per turn (one coil). Our results indicate that the structure becomes more stable with the increase of repeated number of Q, and there is a critical Q number of around 30, above which the structure of the Perutz model is kept stable. In contrast to previous studies, we started molecular dynamics simulations from conformations in which the hydrogen bonds are firmly formed between stacked main chains. This has rendered the initial beta-helix structures of polyQ much more stable for longer time, as compared to those proposed previously. Model calculations for the initial structures of polyQ dimer and tetramer have also been carried out to study a possible mechanism for aggregation.

Independently switchable atomic quantum transistors by reversible contact reconstruction.

The controlled fabrication of actively switchable atomic-scale devices, in particular transistors, has remained elusive to date. Here, we explain the operation of an atomic-scale three-terminal device by a novel switching mechanism of bistable, self-stabilizing reconstruction of the electrode contacts at the atomic level: While the device is manufactured by electrochemical deposition, it operates entirely on the basis of mechanical effects of the solid-liquid interface. We analyze mechanically and thermally stable metallic junctions with a predefined quantized conductance of 1-5 G0 in experiment and atomistic simulation. Atomistic modeling of structural and conductance properties elucidates bistable electrode reconstruction as the underlying mechanism of the device. Independent room temperature operation of two transistors at low voltage demonstrates intriguing perspectives for quantum electronics and logics on the atomic scale.

Investigation of a Kubo-formula-based approach to estimate DNA conductance in an atomistic model.

A novel approach to estimate DNA conductance based upon Kubo formula is presented and discussed. Using this approach, the effects of base pair mismatches, different conformational changes and base pair sequence on DNA electrical properties were investigated. The results were compared with the data from other methods. The new approach makes possible very fast estimation of conductance spectra for oligonucleotides with hundreds of base pairs and can easily be extended to treat arbitrary chemical modifications of DNA.

Localization properties of electronic states in a polaron model of poly(dG)-poly(dC) and poly(dA)-poly(dT) DNA polymers.

We numerically investigate localization properties of electronic states in a static model of poly(dG)-poly(dC) and poly(dA)-poly(dT) DNA polymers with realistic parameters obtained by quantum-chemical calculation. The randomness in the on-site energies caused by the electron-phonon coupling is completely correlated to the off-diagonal parts. In the single electron model, the effect of the hydrogen-bond stretchings, the twist angles between the base pairs and the finite system size effects on the energy dependence of the localization length and on the Lyapunov exponent are given. The localization length is reduced by the influence of the fluctuations in the hydrogen bond stretchings. It is also shown that the helical twist angle affects the localization length in the poly(dG)-poly(dC) DNA polymer more strongly than in the poly(dA)-poly(dT) one. Furthermore, we show resonance structures in the energy dependence of the localization length when the system size is relatively small.

Regular threshold-energy increase with charge for neutral-particle emission in collisions of electrons with oligonucleotide anions.

Electron-DNA anion collisions were studied using an electrostatic storage ring with a merging electron-beam technique. The rate of neutral particles emitted in collisions started to increase from definite threshold energies, which increased regularly with ion charges in steps of about 10 eV. These threshold energies were almost independent of the length and sequence of DNA, but depended strongly on the ion charges. Neutral particles came from breaks of DNAs, rather than electron detachment. The step of the threshold energy increase approximately agreed with the plasmon excitation energy. It is deduced that plasmon excitation is closely related to the reaction mechanism.

Charge Transport in Poly(dG)-Poly(dC) and Poly(dA)-Poly(dT) DNA Polymers.

We investigate the charge transport in synthetic DNA polymers built up from single type of base pairs. In the context of a polaronlike model, for which an electronic tight-binding system and bond vibrations of the double helix are coupled, we present estimates for the electron-vibration coupling strengths utilizing a quantum-chemical procedure. Subsequent studies concerning the mobility of polaron solutions, representing the state of a localized charge in unison with its associated helix deformation, show that the system for poly(dG)-poly(dC) and poly(dA)-poly(dT) DNA polymers, respectively possess quantitatively distinct transport properties. While the former supports unidirectionally moving electron breathers attributed to highly efficient long-range conductivity, the breather mobility in the latter case is comparatively restrained, inhibiting charge transport. Our results are in agreement with recent experimental results demonstrating that poly(dG)-poly(dC) DNA molecules acts as a semiconducting nanowire and exhibit better conductance than poly(dA)-poly(dT) ones.

Folding of oligoglutamines: a theoretical approach based upon thermodynamics and molecular mechanics.

Folding of oligoglutamine chains of different lengths is of crucial interest for exploring the molecular mechanisms of Huntington's disease. A simple oligoglutamine model based upon the Flory-Huggins theory of polymer solutions demonstrates a random coil instability in chains containing more than 40 glutamine residues with respect to beta-sheet formation. This is in striking quantitative agreement with biochemical results on the chain length dependence of polyglutamine aggregation in vivo and in vitro, as well as with clinical data on the polyglutamine chain length dependence of the onset of Huntington's disease. Furthermore, a detailed molecular-mechanical investigation of a polypeptide chain carrying 40 glutamine residues was performed. Two possible folding modes of such an oligoglutamine chain were revealed: a) a beta-hairpin and b) a highly compact random coil entity stabilized by a wealth of H-bonds among the glutamine side chains. A possible role of these folding modes in polyglutamine aggregation, as well as in the onset of Huntington's disease, is discussed.

Huntingtin aggregation monitored by dynamic light scattering.

An initial stage of fibrillogenesis in solutions of glutathione S-transferase-huntingtin (GST-HD) fusion proteins has been studied by using dynamic light scattering. Two GST-HD systems with poly-L-glutamine (polyGln) extensions of different lengths (20 and 51 residues) have been examined. For both systems, kinetics of z-average translation diffusion coefficients (Dapp) and their angular dependence have been obtained. Our data reveal that aggregation does occur in both GST-HD51 and GST-HD20 solutions, but that it is much more pronounced in the former. Thus, our approach provides a powerful tool for the quantitative assay of GST-HD fibrillogenesis in vitro.

Computational support for the suggested contribution of C-H...O=C interactions to the stability of nucleic acid base pairs.

Ab inito quantum chemical calculations are performed to quantify the stabilizing role of long C-H...O=C contacts in nucleic acid base pairing, which was suggested by Leonard, McAuley-Hecht, Brown & Hunter [(1995). Acta Cryst. D51, 136-139]. For the Watson-Crick adenine-uracil pair, a contribution of about 6% to the total bond energy is obtained. This weakly bonding effect is primarily a result of electrostatic attraction between the total positive charge of adenine C(2)-H and the negative end of the dipole uracil O(2)=C.

Theoretical analysis of deoxycytidine-5'-phosphate protonation.

The electron density distribution in deoxycytidine-5'-monophosphate (5'-dCMP) molecule and dianion has been studied by the method of CNDO/2. The comparison between the results of calculation for the neutral molecule and the data obtained by Pearlman and Kim shows that there is a linear correlation between the atomic charges calculated using quantum chemistry and those derived from X-ray results. However, partial charges for the deoxyribose fragment are correlated in a nonlinear manner. The influence of the protons added to the cytosine and phosphate residues on the atomic charges and bond orders of deoxy-cytidine-5'-monophosphate has been analyzed here. The conclusion has been drawn that the semiempirical quantum-chemical CNDO/2 technique is applicable to the mononucleotide studies.