Modelling RNA folding under mechanical tension

We investigate the thermodynamics and kinetics of RNA unfolding and refolding under mechanical tension. The hierarchical nature of RNA structure and the existence of thermodynamic parameters for base pair formation based on nearest-neighbour interactions allows modelling of sequence-dependent folding dynamics for any secondary structure. We calculate experimental observables such as the transition force for unfolding, the end-to-end distribution function and its variance, as well as kinetic information, for a representative RNA sequence and for a sequence containing two homopolymer segments: A.U and G.C.     

RNA分子折叠的统计力学

RNA分子折叠对决定分子（基因）水平上的生命活动是至关重要的．文章对RNA分子折叠（特别是二级结构的折叠）的热力学和动力学性质作一简单回顾与介绍．因为静电相互作用在RNA折叠过程中的特殊重要作用，文章作者对RNA（与DNA）折叠的电相互作用单独作较为详细的讨论．     

An Insight into the Helicase Functioning Through the Hydrogen Isotope Effects

The replacement of hydrogen atoms by deuterium in hydrogen bonds of base pairs AT and GC decreases the rate of unwinding DNA by more than 30% per each unzipped base pair. In active helicases this isotope effect refers to the ratio of the rate constants for unzipping closed base pairs in protiated and deuterated DNA. In passive helicases the effect is controlled by ratio of equilibrium constants for opening and closing base pairs in protiated and deuterated DNA. Hydrogen/deuterium isotope effects on the unwindening of double strand DNA seems to explain, at least partly, biological and pharmacological effects of heavy water on living organisms and may be used as a means to explore new facets of the helicase functioning.     

Coupled dynamics of RNA folding and nanopore translocation

The translocation of structured RNA or DNA molecules through narrow pores necessitates the opening of all base pairs. Here, we study the interplay between the dynamics of translocation and base pairing theoretically, using kinetic Monte Carlo simulations and analytical methods. We find that the transient formation of base pairs that do not occur in the ground state can significantly speed up translocation.     

Modeling DNA beacons at the mesoscopic scale

We report model calculations on DNA single strands which describe the equilibrium dynamics and kinetics of hairpin formation and melting. Modeling is at the level of single bases. Strand rigidity is described in terms of simple polymer models; alternative calculations performed using the freely rotating chain and the discrete Kratky-Porod models are reported. Stem formation is modeled according to the Peyrard-Bishop-Dauxois Hamiltonian. The kinetics of opening and closing is described in terms of a diffusion-controlled motion in an effective free-energy landscape. Melting profiles, dependence of melting temperature on loop length, and kinetic time scales are in semiquantitative agreement with experimental data obtained from fluorescent DNA beacons forming poly(T) loops. Variation in strand rigidity is not sufficient to account for the large activation enthalpy of closing and the strong loop length dependence observed in hairpins forming poly(A) loops. Implications for modeling single strands of DNA or RNA are discussed.     

Kinetic barriers in RNA unzipping

We consider a simple model for the unfolding of RNA tertiary structure under dynamic loading. The opening of such a structure is regarded as a two step process, each corresponding to the overcoming of a single energy barrier. The resulting two-barrier energy landscape accounts for the dependence of the unfolding kinetics on the pulling rate. Furthermore at intermediate force, the two barriers cannot be distinguished by the analysis of the opening kinetic, which turns out to be dominated by a single macro-barrier, whose properties depend non-trivially on the two single barriers. Our results suggest that in pulling experiments on RNA molecule containing tertiary structures, the details of the single kinetic barriers can only be obtained using a low pulling rate value, or in the high force regime.Received: 19 January 2004, Published online: 12 July 2004PACS: 87.14.Gg DNA, RNA - 82.37.-j Single molecule kineticsL. Peliti: Associato INFN, Sezione di Napoli     

Changes in the zero-point energy of the protons as the source of the binding energy of water to A-phase DNA

The measured changes in the zero-point kinetic energy of the protons are entirely responsible for the binding energy of water molecules to A phase DNA at the concentration of 6 water molecules/base pair. The changes in kinetic energy can be expected to be a significant contribution to the energy balance in intracellular biological processes and the properties of nano-confined water. The shape of the momentum distribution in the dehydrated A phase is consistent with coherent delocalization of some of the protons in a double well potential, with a separation of the wells of 0.2??.     

Stretching and relaxation dynamics in double stranded DNA

We study numerically the mechanical stability and elasticity properties of duplex DNA molecules within the frame of a network model incorporating microscopic degrees of freedom related with the arrangement of the base pairs. We pay special attention to the opening–closing dynamics of double-stranded DNA molecules which are forced into non-equilibrium conformations. Mechanical stress imposed at one terminal end of the DNA molecule brings it into a partially opened configuration. We examine the subsequent relaxation dynamics connected with energy exchange processes between the various degrees of freedom and structural rearrangements leading to complete recombination to the double-stranded conformation. The similarities and differences between the relaxation dynamics for a planar ladder-like DNA molecule and a twisted one are discussed in detail. In this way we show that the attainment of a quasi-equilibrium regime proceeds faster in the case of the twisted DNA form than for its thus less flexible ladder counterpart. Furthermore we find that the velocity of the complete recombination of the DNA molecule is lower than the velocity imposed by the forcing unit which is in compliance with the experimental observations for the opening–closing cycle of DNA molecules.     

Nonlinear fluctuation phenomena in the transport properties of superconductors

There exists a wide temperature region $(GiT < T - T_c < T\sqrt {Gi} )$ where the influence of fluctuations on the thermodynamic properties of superconductors can be taken into account in the linear (Gaussian) approximation, while their influence on the kinetic properties is strongly nonlinear. The Maki-Thompson contribution to the conductivity saturates in this region. However, the Aslamazov-Larkin contribution becomes even more singular. This enhancement is related to the fact that nonlinear effects increase the lifetime of fluctuating pairs. The pair breaking and energy relaxation processes can decrease the nonlinear effects.     

The relationship between kinetic and thermodynamic fragilities in metallic glass-forming liquids

The correlation between the temperature dependence of the kinetic and thermodynamic properties of a series of metallic glass-forming liquids is investigated using the concept of fragility. The results indicate a correlation between the kinetic fragility and thermodynamic fragility in these liquids. The correlation depends critically on the approach used to evaluate the thermodynamic fragility. Two distinct correlation lines are found for the metal–metalloid and for the all-metallic-constituents glass-forming liquids. For the same thermodynamic fragility the metal–metalloid liquids exhibit a distinctively larger kinetic fragility than the pure-metallic liquids. From the evaluation of the Gibbs free-energy difference between the undercooled liquid and the crystalline phase mixture, a correlation between the kinetic fragility and the driving force for nucleation is found, showing that for glass formation in metallic alloys the thermodynamic and kinetic contributions act together.     

A continuum model of gas flows with localized density variations

We discuss the kinetic representation of gases and the derivation of macroscopic equations governing the thermomechanical behavior of a dilute gas viewed at the macroscopic level as a continuous medium. We introduce an approach to kinetic theory where spatial distributions of the molecules are incorporated through a mean-free-volume argument. The new kinetic equation derived contains an extra term involving the evolution of this volume, which we attribute to changes in the thermodynamic properties of the medium. Our kinetic equation leads to a macroscopic set of continuum equations in which the gradients of thermodynamic properties, in particular density gradients, impact on diffusive fluxes. New transport terms bearing both convective and diffusive natures arise and are interpreted as purely macroscopic expansion or compression. Our new model is useful for describing gas flows that display non-local-thermodynamic-equilibrium (rarefied gas flows), flows with relatively large variations of macroscopic properties, and/or highly compressible fluid flows.     

Image enhancement through contrast enlargement using the image regions extracted by multiscale top-hat by reconstruction

An image enhancement algorithm based on multiscale top-hat by reconstruction is proposed in this paper. Firstly, multiscale top-hat by reconstruction using multiscale structuring elements is discussed. Then, multiscale bright and black image regions are extracted. Thirdly, useful image regions for image enhancement are obtained from the extracted multiscale bright and black image regions. Finally, after a base image is calculated from the results of the opening and closing by reconstruction operations, the original image is enhanced through combing the useful image regions into the base image. Experimental results on different types of images show that the proposed algorithm is efficient.     

Thermal denaturation of DNA molecules: A comparison of theory with experiment

Experimental and theoretical results on the helix-coil transition of DNA are reviewed. The theoretical model of the transition is described, and the influence of heterogeneous base pair stacking, and strand dissociation on the predicted melting transition is examined. New experimental transition data on seven DNAs, 154–587 base pairs (bp) long, are reported and compared with theoretical calculations. We review and evaluate previous studies on long DNAs (≥1000 bp) as well as previous and recent results on short DNAs. The comparison of theory with equilibrium melting curves of short DNAs indicates that base pair sequence has a relatively small influence on the stacking free energy. Excellent agreement is obtained between theory and equilibrium transitions of 14 out of 15 fragments 80–587 pb. The deviation between theory and experiment for a 516 bp DNA can be attributed to the formation of stem-loop structures. This may provide the explanation for inconsistent results observed with long DNAs. The effect of single base pair changes on DNA transitions is discussed. Current views on fluctuational opening of base pairs at temperatures below the transition are described.     

Effect of an external action on a pair distribution function in a steady state

An external action that reduces a two-component equilibrium thermodynamic system to a nonequilibrium steady state with scalar fluxes has been studied. A system of integrodifferential equations for pair correlation functions has been obtained. These equations coincide with the second equations of the Bogoliubov-Born-Green-Kirkwood-Yvon hierarchy, but with different effective temperatures. Thus, ordinary integrodifferential equations for a pair correlation function with effective temperatures expressed in terms of the perturbed (nonequilibrium) Maxwellian momentum distribution function can be used to calculate the structural and thermodynamic properties of such a system.     

The possibility of using RNA for optical applications

Based on computer simulation, it is proposed that so-called RNA nanotubes, which are sequences of bonded RNA nanorings, be used for optical applications in manufacturing metamaterials. A recently developed model of coarse-grained RNA is used that allows the study of key properties of RNA nanotubes. The Langevin method is used to discover the basic thermodynamic and mechanical properties of nanotubes and their response to an external field.     

Rotational drag on DNA: a single molecule experiment

Within a single-molecule configuration, we have studied rotational drag on double stranded linear DNA by measuring the force during mechanical opening and closing of the double helix at different rates. The molecule is cranked at one end by the effect of unzipping and is free to rotate at the other end. In this configuration the rotational friction torque tau on double-stranded DNA leads to an additional contribution to the opening force. It is shown that the effect of rotational drag increases with the length of the molecule, is approximately proportional to the angular velocity of cranking, and we estimate that the torque tau is of the order of 1k(B)T for 10 000 base pairs of DNA cranked at 2000 turns per second.     

Two-dimensional random walk and characteristics of helix-coil transition in DNA

On the basis of two-dimensional random walk model, a model of melting of double-stranded DNA is proposed. The expressions for the free energy, the helicity degree and the correlation function of nitrogenous base pair formation, remoted along the chain, are obtained. The temperature dependence of thermodynamic parameters of the model is analyzed. It is shown that the temperature dependence of the helicity degree is qualitatively similar to those obtained in experiments. It is established that the correlation function decays exponentially with increasing distance along the chain between the base pairs.     

高压下液态硝基甲烷的分子动力学模拟

 对高压下液态硝基甲烷的性质进行经典和基于第一性原理计算的Car-Parrinello分子动力学（CPMD）模拟。利用经典势的分子动力学（MD）模拟研究了高压压缩状态下液态硝基甲烷的结构和热力学性质,得到了高达14.2 GPa压力下的理论Hugoniot数据。对于一些热力学函数,如总能和粒子速度,经典势模拟给出了很好的总趋势,基本特征和实验观测一致。但是在给定的密度下,经典模拟预言的Hugoniot压力偏高。在几个选定的密度下,进行了CPMD模拟,得到了二体相关函数、速度自相关函数、振动光谱和其它的热力学性质,并与经典模拟结果进行了比较。对二体相关函数的分析表明经典势的短程部分的刚性可能太强,从而导致了比实验值高的理论压力值。对于某些二体相关函数,CPMD模拟和经典模拟结果差别很大,可以归结为量子效应。当压力增高时,量子模拟得到的振动光谱向高频部分移动的现象与实验观测相符合。     

Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma

Toward the expansion of the genetic alphabet of DNA, several artificial third base pairs (unnatural base pairs) have been created. Synthetic DNAs containing the unnatural base pairs can be amplified faithfully by PCR, along with the natural A-T and G-C pairs, and transcribed into RNA. The unnatural base pair systems now have high potential to open the door to next generation biotechnology. The creation of unnatural base pairs is a consequence of repeating "proof of concept" experiments. In the process, initially designed base pairs were modified to address their weak points. Some of them were artificially evolved to ones with higher efficiency and selectivity in polymerase reactions, while others were eliminated from the analysis. Here, we describe the process of unnatural base pair development, as well as the tests of their applications.(Communicated by Takao SEKIYA, M.J.A.).