Simulation of DNA bases in water: Comparison of the Monte Carlo algorithm with molecular mechanics force fields

The interaction between the nucleic acid bases and solvent molecules has an important effect in various biochemical processes. We have calculated total energy and free energy of the solvation of DNA bases in water by Monte Carlo simulation. Adenine, guanine, cytosine, and thymine were first optimized in the gas phase and then placed in a cubic box of water. We have used the TIP3 model for water and OPLS for the nucleic acid bases. The canonical (T, V, N) ensemble at 25 degrees C and Metropolis sampling technique have been used. Good agreement with other available computational data was obtained. Radial distribution functions of water around each site of adenine, guanine, cytosine, and thymine have been computed and the results have shown the ability of the sites for hydrogen bonding and other interactions. The computations have shown that guanine has the highest value of solvation free energy and N7 and N6 in adenine and guanine, N3 in cytosine, and N3 and O4 in thymine have the largest radial distribution function. Monte Carlo simulation has also been performed using the CHARMM program under the same conditions, and the results of two procedures are compared.     

方差组分估计方法MIVQUE和REML的模拟比较

利用ＭｏｎｔｅＣａｒｌｏ方法,对４种数据结构进行了ＭＩＶＱＵＥ和ＲＥＭＬ两种方差组分估计方法的模拟比较。方差组分估计所用的模型为奶牛育种中常用的公畜模型,它包括场年季固定效应、公牛组固定效应和公牛随机效应。４种数据结构中最大的有１２８４７个观察值,场年季效应和公牛效应水平数分别为７７８和４７,它与北京市目前可利用的奶牛头胎产奶量记录资料相当。最小的数据结构只有２００个观察值,１４８个场年季和２０头公牛。比较指标为估计值的偏差和方差（理论的或根据１０００次重复模拟所得的经验值）。结果表明,对于较大样本的数据结构,两种方法差异很小,它们间的估计值的相关接近于１,偏差小于真值的１％,方差近似相等。对于较小样本的数据结构,ＭＩＶＱＵＥ则明显优于ＲＥＭＬ。本研究还表明,对于ＲＥＭＬ来说,类似数据结构１的样本已能满足其渐近无偏性和有效性的大样本特性。     

Nature of the stacking of nucleic acid bases in water: a Monte Carlo simulation

The results of a Monte Carlo simulation of the hydration of uracil and thymine molecules, their stacked dimers and hydrogen-bonded base pairs are presented. Simulations have been performed in a cluster approximation. The semiempirical atom-atom potential functions have been used (cluster consisting of 200 water molecules). It has been shown that the stacking interactions of uracil and thymine molecules in water arise mainly due to the increase in the water-water interaction during the transition from monomers to dimer. It has been found out that stacked base associates are more preferable than base pairs in water. This preference is mainly due to the energetically more favourable structure of water around the stack.     

Lac Repressor Mediated DNA Looping: Monte Carlo Simulation of Constrained DNA Molecules Complemented with Current Experimental Results

Tethered particle motion (TPM) experiments can be used to detect time-resolved loop formation in a single DNA molecule by measuring changes in the length of a DNA tether. Interpretation of such experiments is greatly aided by computer simulations of DNA looping which allow one to analyze the structure of the looped DNA and estimate DNA-protein binding constants specific for the loop formation process. We here present a new Monte Carlo scheme for accurate simulation of DNA configurations subject to geometric constraints and apply this method to Lac repressor mediated DNA looping, comparing the simulation results with new experimental data obtained by the TPM technique. Our simulations, taking into account the details of attachment of DNA ends and fluctuations of the looped subsegment of the DNA, reveal the origin of the double-peaked distribution of RMS values observed by TPM experiments by showing that the average RMS value for anti-parallel loop types is smaller than that of parallel loop types. The simulations also reveal that the looping probabilities for the anti-parallel loop types are significantly higher than those of the parallel loop types, even for loops of length 600 and 900 base pairs, and that the correct proportion between the heights of the peaks in the distribution can only be attained when loops with flexible Lac repressor conformation are taken into account. Comparison of the in silico and in vitro results yields estimates for the dissociation constants characterizing the binding affinity between O1 and Oid DNA operators and the dimeric arms of the Lac repressor.     

The bridge between first-principles calculations and grand canonical Monte Carlo simulations: Morse and Lennard-Jones force fields

We use the modelled adsorbate (methane) and adsorbent (carbon nanotube) to explore the choice of site-to-site force fields in order to bridge the gap between first-principles calculation and grand canonical Monte Carlo. By using the mature classical Lennard-Jones potential-based results as benchmark, it is found if the first-principles calculation is performed at the higher MP2/6-311G** level, Morse potential model should be adopted to achieve the force field parameters. It is expected that this work provides useful information for the building of the multiscale simulation method and the selection of accurate force field models.     

Monte Carlo simulation of the water in a channel with charges.

A Monte Carlo simulation of water in a channel with charges suggests the existence of water in immobile, high density, essentially glasslike form near the charges. The channel model has a conical section with an opening through which water molecules can pass, at the narrow end of the cone, and a cylindrical section at the other end. When the charges are placed near the narrow section of the model, the "glass" effectively blocks the channel; with the charges removed, the channel opens. The effect can be determined from the rate of passage of the water molecules through the pore, from the average orientation of the water molecule, and from distortion of the distribution of molecules. In the simulations carried out to date, no external ions have been considered. In addition to the energy, the Helmholtz free energy has been calculated.     

Monte Carlo simulation of early molecular evolution in the RNA World

The origin of life remains a highly speculative field, mainly due to the shortage of our knowledge on prebiotic chemistry and basic understanding on the essence of life. In this context, computer simulation is expected to play an important role. For instance, the scenario concerning the genesis of the widely accepted RNA World remains blurry, though we have gathered some circumstantial evidence and fragmented knowledge on several supposed stages, including formation of polynucleotides from a prebiotic nucleotide pool, emergence of RNA replicases (RNA molecules catalyzing their own replication), and evolution of RNA replicases. It is highly valuable to simulate the stages as a continuous process to evaluate the plausibility of the supposition and study the rules involved. Here we construct a computer simulation on the process using Monte Carlo method. It demonstrates that primordial RNA replicases may appear and spread in a nucleotide pool provided they could recognize their own sequence and their complements as catalytic targets, and then may evolve to more efficient RNA replicases. Apart from its indication on the genesis of the RNA World, the vivid simulation of emergence of the “first replicative molecules” and their subsequent evolution is impressive and may help to get insight into “how could self-replication and Darwinian evolution, two key features of life, emerge in a non-life background?” thus improve our understanding of “what is life” when studying origins of life.     

Monte Carlo Simulation of Fluids in Curved Three-dimensional Space

Abstract

This work describes the methods required to perform computer simulations of three-dimensional fluids confined to the surface of a four-dimensional hypersphere. The use of such non-Euclidian spaces, or spherical boundary conditions, is convenient in cases where spatial inhomogeneities occur over length-scales comparable to that of the entire system. The form of the pressure equation in curved space is discussed, and the results of Monte Carlo simulations of hard spheres confined to the surface of a hypersphere are presented. Comparison of the simulation results to the Carnahan-Starling equation of state in flat space provides a basis for determining when curvature effects can be neglected.     

A fast Monte Carlo algorithm to simulate the spectrum of DNA damages formed by ionizing radiation

Ionizing radiation produces both singly and multiply damaged DNA sites. Multiply damaged sites (MDS) have been implicated in radiation-induced cell killing and mutagenesis. The spatial distribution of elementary damages (strand breaks and base damages) that constitute MDS is of special interest, since the complexity of MDS has an impact on damage repair. A fast and easy-to-implement algorithm to simulate the local clustering of elementary damages produced by ionizing radiation is proposed. This algorithm captures the major trends in the DNA damage spectrum predicted using detailed track- structure simulations. An attractive feature of the proposed algorithm is that only four adjustable parameters need to be identified to simulate the formation of DNA damage. A convenient recipe to determine the parameters used in the fast Monte Carlo damage simulation algorithm is provided for selected low- and high-LET radiations. The good agreement among the damage yields predicted by the fast and detailed damage formation algorithms suggests that the small-scale spatial distribution of damage sites is determined primarily by independent and purely stochastic events and processes.     

Ions around DNA: Monte Carlo estimates of distribution with improved electrostatic potentials

Coulomb's law for the electrostatic interactions between ions is modified when discontinuities in dielectric constant (relative permittivity) occur. In a DNA solution such a discontinuity occurs at the interface between the DNA molecular helix and the surrounding water. We take the modified interaction potentials from a previous report [Macromolecules (1986) 19 , 1186–1194] and use them with the Monte Carlo method to find the distribution of univalent and bivalent counterions around the DNA helix in the absence of coions (i.e., no added salt). In comparing the ion distribution with the modified potential to the distribution without, we find that the effects of the modifications to the potentials are considerable. The modifications tend to drive the ions out of the grooves of the helix, especially out of the major groove. This result comes partly from the repulsion exerted on the ions by the low-permittivity helix and partly from the concentration of the field of the phosphates at the surface of the helix, a concentration that is also caused by the discontinuity in permittivity.     

On the molecular mechanism of liver alcohol dehydrogenase: Monte Carlo simulations and X-ray studies of water in the substrate channel

Water structure in the substrate channel of liver alcohol dehydrogenase as a function of the oxidation state of the coenzyme nicotinamide ring has been studied with Monte Carlo simulations. X-ray data on water structure has been analyzed. The simulations show an order-disorder effect in the water distribution produced by the charge state of the ring; also, solvation-desolvation effects are detected. For positively charged ring, the water molecules form a fluctuated H-bonded network that connects the deeply buried active site zinc to the bulk solvent. This network together with the side chain of Ser-48 most likely is the support for a proton relay system thereby providing a mechanism responsible of the pKa shift of the zinc-bound water as it is produced by the oxidized coenzyme binding.     

蒙特卡罗法在化感作用全区间抑制强度评估(wholerange assessment)中的应用

植物化感作用的强弱与化感物质的作用浓度相关.化感作用全区间抑制强度指数(Whole-range assessmentindex)是用于评估植物在一定的化感物质作用范围内所受化感作用总体抑制程度的一种方法.在对非线性剂量响应进行曲线拟合的基础上,本研究应用蒙特卡罗模拟法为计算化感作用全区间抑制强度指数提供了一种科学的数学计算方法,并应用该计算方法分析了番茄水浸提液对生菜、萝卜、白菜、菜心、包心菜、豆角和水稻的化感作用强度.     

Monte Carlo Simulation of Hydration of the Nucleic Acid Fragments

Abstract

Systems containing a base or a base pair and 25 water molecules, as well as a helical stack and 30 water molecules per base pair, have been simulated. Changes in the base hydration shell structure, after the bases have been included into the pair and then into the base pair stack are discussed. Hydration shells of several configurations of the base pair stacks are discussed. Probabilities of formation of the hydrogen-bonded bridges of 1, 2 and 3 water molecules between hydrophilic centres have been estimated. The hydration shell structure was shown to depend on the nature of the base pair and on the stack configuration, while dependence of the global hydration shell characteristics on the stack configuration has been proved to be rather slight. The most typical structural elements of hydration shells, in the glycosidic (minor in B-like conformation) and non-glycosidic (major) grooves, for different configurations of AU and GC stacks, have been found and discussed. The number of hydrogen bonds between water molecules and bases per water molecule was shown to change upon transformation of the stack from A to B configuration. This result is discussed in connection with the reasons for B to A conformational transition and the concept of “water economy”. Hydration shell patterns of NH₂-groups of AU and GC helical stacks differ significantly.     

Monte Carlo Simulation of Nonionic Surfactants at the Oil-Water Interface

Abstract

A Monte Carlo simulation method has been developed for modelling amphiphiles at an oil-water interface. Properties are calculated for the mixture water, benzene and tetraoxyethylene glycol dodecyl ether.     

Hydration of Uracil and Thymine Methylderivatives: a Monte Carlo Simulation

Abstract

The simulation performed shows that under methylation of uracil and thymine NH-groups the interaction energy between a base and water (U_wb) is increased. It is also detected that the increase in this energy was observed in the 1st and the 3rd sectors. These conclusions do not confirm the assumption made in the literature on the character of an interaction between methylated bases and water. According to this assumption, when the NH-groups are methylated, the energy of U_wb in these sectors decreases as a result of the van der Waals interactions between a methyl group and water, whose energy compensates the increase in the U_wb energy due to the breaking of an H-bond. Regularity of water molecules near a hydrophobic group under the hydration of polar molecules is detected for the first time.     

Monte Carlo Simulation of Binary Gas Adsorption in Zeolite Cavities

Abstract

Grand canonical Monte Carlo simulations have been performed for binary adsorption of Lennard-Jones molecules with point multipole moments in zeolite cavities of type X. Fluid-solid electrostatic interactions were taken into account. Phase diagrams and total coverage were calculated for three binaries and compared with experimental measurements. MC simulations gave good agreement with experiment for two mixtures (C₂H₄-CO₂ and CO₂-CH₄) but there were discrepancies between simulation and experiment for the system i-C₄H₁₀-C₂H₄. The dependence of excess Gibbs free energy on the composition and pressure was studied. Negative deviations from ideality are due to energetic heterogeneity and size effects. Unlike liquid-vapor equilibrium, deviations from the Lorentz-Berthelot mixing rules for the adsorbates have little effect upon the phase behavior. Density distributions show that the components compete for the high energy sites inside the cavity; depending on its relative strength of adsorption, one component may be excluded from such positions (CH₄ in CO₂-CH₄), or the two species may share sites inside the cavity (C₂H₄-CO₂).     

Stillinger-Weber Type Potentials in Monte Carlo Simulation of Amorphous Silicon

The growth of amorphous silicon on a substrate of a two-layer slab of crystalline silicon with various surface indices is simulated with Stillinger-Weber type interatomic potentials. The growth is realized by means of a continuum Monte Carlo method and the radial distribution functions are evaluated for various cases.