Data Mining of Molecular Dynamics Trajectories of Nucleic Acids

Abstract

Analysis, storage, and transfer of molecular dynamic trajectories are becoming the bottleneck of computer simulations. In this paper we discuss different approaches for data mining and data processing of huge trajectory files generated from molecular dynamic simulations of nucleic acids.     

Minimum Image Convention Coding of Microcomputers

Abstract

Whenever computer simulations on fluids are performed with periodic (cubic) boundary conditions, one of the most frequently performed numerical operations is the calculation of the distance between a given molecule and the nearest image of a neighbour particle. Often this is accomplished by a computer code.     

Multishelled Gold Nanowires

Abstract

The current miniaturization of electronic devices raises many questions about the properties of various materials at nanometre-scales. Recent molecular dynamics computer simulations have shown that small finite nanowires of gold exist as multishelled structures of lasting stability. These classical simulations are based on a well-tested embedded atom potential. Molecular dynamics simulation studies of metallic nanowires should help in developing methods for their fabrication, such as electron-beam litography and scanning tunneling microscopy.     

Solution Influence on Biomolecular Equilibria: Nucleic Acid Base Associations

Abstract

This paper consists of two parts. In the first part, the general problem of biomolecular equilibria in solution is considered, stressing that molecular interactions ultimately determine the answer to this problem. It is discussed how computer simulation techniques can reliably treat the problem and several pitfalls of computer simulation to be avoided are pointed out. Other approaches based on modeling and conceptual simplifications such as perturbative methods, long-range interaction approximations, surface thermodynamic approaches, and hydration shell models are discussed. In the second part, the results of Monte Carlo calculations on the associations of nucleic acid bases in water and carbon tetrachloride are presented. Stacked self-associations are found to be preferred in water and hydrogen-bonded complexes are favored in nonpolar solutions, in agreement with experimentell data. The influence of the solvent on base associations is explained in terms of solute-solvent and solvent-solvent contributions to the total energy. No enthalpic stabilization of the complexes by the solvent was found. The results are used to examine the validity of various approximations discussed in the first part of the paper.     

A Computer Simulation of the Adsorption and Diffusion of Benzene and Toluene in the Zeolites Theta-1 and Silicalite

Abstract

The influence of the framework geometries of zeolites on the adsorption and diffusion of benzene and toluene molecules has been studied through computer simulations. The behaviours of the uni- and bi-dimensional pore zeolites, theta-1 and silicalite, respectively, have been compared.     

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.     

Comparison of Different Three-site Interaction Potentials for Liquid Acetonitrile

Abstract

Computer simulations of liquid acetonitrile at normal room conditions are reported. Both static and dynamic properties are analysed. Special attention is paid to the dielectric properties. A three-site interaction potential has been derived from ab initio calculations on the gas phase dimer and a comparison with different three-site interaction potentials available in the literature is presented. The suitability of three-site models to reproduce the properties of the real liquid is discussed by comparing computer simulation results with experimental data.     

A Molecular Dynamics Computer Simulation Performance Comparison of Java Versus C

Abstract

The relative performance of molecular dynamics (MD) computer simulations of fluids written in ANSI C is compared to that achieved by a comparable program written in Java. The performance of the Java program is shown to be dependent upon its runtime environment. The Java Runtime Environment (JRE) from the Java Development Kit (JDK) 1.2 provides a Just-In-Time (JIT) compiler option on Solaris and Windows 95 platforms which decreases the execution time by approximately 4–10× compared to the standard Java interpreter. The compiled Java implementation of the MD computer simulation runs between 30–100% slower. depending on the platform, compared to the equivalent C implementation. The stability of the two simulations, as measured by conservation of energy is shown to be identical to within ～ 1% over 10⁵ time steps.     

Efficient Test Molecule Sampling in Molecular Simulation

Abstract

Excluded volume map sampling (EVMS) is a particularly efficient means of performing test molecule sampling to estimate or impose chemical potential in molecular simulations. This paper discusses the motivation and applications of excluded volume map sampling, presents computer code demonstrating its implementation, and gives an example of its application.     

Numerical Calculation of the Bridge Function for Soft-Sphere Supercooled Fluids via Molecular Dynamics Simulations

Abstract

Isokinetic molecular dynamics simulations have been performed for 13,500 soft-spheres interacting through the inverse-power potential, ε([sgrave]/r)ⁿ , near and below the freezing temperature. The bridge function for the integral equation of the theory of liquids is extracted from the pair distribution function (PDF) obtained by the computer simulations for n = 6 and 12. The result is compared with that of approximate theories, i.e., the Rogers-Young (RY) approximation and a modified hypernetted-chain approximation for supercooled soft-sphere fluids (MHNCS approximation). Below the freezing temperature, the bridge function obtained by the computer simulation begins to oscillate around zero at intermediate distances where the second peak of the PDF appears. Such oscillatory behavior of the bridge function is well reproduced by the MHNCS approximation which includes correlations given by the leading elementary diagram, in remarkable contrast to that of the RY approximation. The present result suggests that the split second peak of the PDF for highly supercooled liquids is essentially dominated by the intermediate-distance-range correlation of the leading elementary diagram.     

Generation and study of a relatively large amorphous silica surface in the liquid phase

Through the classical and ab-initio molecular dynamics computer simulations, the aim of this study was to generate and analyse a surface-type structure in the liquid phase at a temperature of 3400?K. First, a crystalline structure was used (β-cristobalite) with 216 SiO₂ molecules (648 atoms) and it was melted. Next, the resulting structure was properly cut, with a total of 546 particles remaining, and this system was put into a geometric arrangement denominated ‘sandwich’, where it was equilibrated. The prior processes were implemented through the classical molecular dynamics computer simulations using the effective classical potential of Feuston [B. P. Feuston and S. H. Garofalini, J. Chem. Phys. 89, 5818 (1988)]. Finally, the electronic charge distribution and topological and bonding defects were analysed in the first five superior layers of this system. This latter was carried out through the ab-initio molecular dynamics computer simulations, where the pseudopotentials of N. Trouiller and J. L. Martins [N. Trouiller, J. L. Martins, Phys. Rev. B 43, 1993 (1991)] were used. The results show different aspects between them, the interaction between the bonding and topological defects, and the existence of two-membered rings, nonbridging oxygens (NBOs) and three-coordinated silicon at the outermost surface.     

Some Aspects of the Biology of Pilaira anomala—An Extremely Versatile Fungus

Abstract

This article describes the rationale for mathematical modelling and computer simulation of ecological systems, and suggests reasons why this is still a relatively unexplored field of biological education. Recently, inexpensive yet extremely versatile modular analogue computing systems have become available from UK suppliers of science teaching equipment. These are suggested as possible alternatives to digital machines for those wishing to introduce modelling and simulation into their teaching. The behaviour of an analogue computer and the operations it performs are described. The application of these ideas to the teaching of population ecology is then illustrated through analogue simulations of exponential growth, logistic growth, and predator-prey interactions. Typical results for each of these three models are presented.     

100ps Molecular Dynamic Simulation of d(TATCACC)2

Abstract

A heptanucleotide sequence d(TATCACC)2 from OR3 region of bacteriophage X is considered sufficient for the recognition of Cro protein. We present here results on molecular dynamic simulations on this sequence for 100 ps in 0.02 ps interval. The simulations are done using computer program GROMOS. The conformational results are averaged over each ps. The IUPAC torsional parameters for 100 conformations are illustrated using a wheal and a dial systems. Several other stereochemical parameters such as H-bonding lengths and angles, sugar puckers, helix twist and roll angles as also distances between opposite strand phosphorus are depicted graphically. We find that there is rupture of terminal H-bonds. The bases are tilted and shifted away from the helix axis giving rise to bifurcated H-bonds. H- bonds are seen even in between different base pairs. The role of these dynamic structural changes in the recognition of OR3 operator by Cro protein is discussed in the paper.     

Systolic Loop Methods for Molecular Dynamics Simulation,Generalised for Macromolecules

Abstract

Systolic loop programs have been shown to be very efficient for molecular dynamics simulations of liquid systems on distributed memory parallel computers. The original methods address the case where the number of molecules simulated exceeds the number of processors used. Simulations of large flexible molecules often do not meet this condition, requiring the three- and four-body terms used to model chemical bonds within a molecule to be distributed over several processors. This paper discusses how the systolic loop methods may be generalised to accommodate such systems, and describes the implementation of a computer program for simulation of protein dynamics. Performance figures are given for this program running typical simulations on a Meiko Computing Surface using different number of processors.     

Differential interactions of the antimicrobial peptide,RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes

BackgroundAntimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus.MethodsA physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations.ResultsRQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces.ConclusionsRQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application.General significanceThese results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces.     

mbs: modifying Hudson's ms software to generate samples of DNA sequences with a biallelic site under selection

Background  

The pattern of single nucleotide polymorphisms, or SNPs, contains a tremendous amount of information with respect to the mechanisms of the micro-evolutionary process of a species. The inference of the roles of these mechanisms, including natural selection, relies heavily on computer simulations. A coalescent simulation is extremely powerful in generating a large number of samples of DNA sequences from a population (species) when all mutations are neutral, and Hudson's ms software is frequently used for this purpose.     

Validation of Bayesian analysis of compartmental kinetic models in medical imaging

IntroductionKinetic compartmental analysis is frequently used to compute physiologically relevant quantitative values from time series of images. In this paper, a new approach based on Bayesian analysis to obtain information about these parameters is presented and validated.Materials and methodsThe closed-form of the posterior distribution of kinetic parameters is derived with a hierarchical prior to model the standard deviation of normally distributed noise. Markov chain Monte Carlo methods are used for numerical estimation of the posterior distribution. Computer simulations of the kinetics of F18-fluorodeoxyglucose (FDG) are used to demonstrate drawing statistical inferences about kinetic parameters and to validate the theory and implementation. Additionally, point estimates of kinetic parameters and covariance of those estimates are determined using the classical non-linear least squares approach.Results and discussionPosteriors obtained using methods proposed in this work are accurate as no significant deviation from the expected shape of the posterior was found (one-sided P > 0.08). It is demonstrated that the results obtained by the standard non-linear least-square methods fail to provide accurate estimation of uncertainty for the same data set (P < 0.0001).ConclusionsThe results of this work validate new methods for a computer simulations of FDG kinetics. Results show that in situations where the classical approach fails in accurate estimation of uncertainty, Bayesian estimation provides an accurate information about the uncertainties in the parameters. Although a particular example of FDG kinetics was used in the paper, the methods can be extended for different pharmaceuticals and imaging modalities.     

Anisotropic Site-Site Potentials in Molecular Dynamics

Abstract

This paper describes techniques for calculating the forces and torques for molecular simulations that use anisotropic site-site potentials. The general techniques are illustrated for pairs of linear and tetrahedral molecules. A technique for combining anisotropic site-site potentials with constraint dynamics is described. These ideas are tested by simulating an anisotropic site-site potential model for the non-bonded interactions in liquid butane. This model is as accurate as the all-atom Williams potential from which it is derived but can be simulated using approximately half the computer time of the all-atom potential. Anisotropic site-site potentials offer a flexible and cost-effective method of simulating a range of hydrocarbon systems.     

Gibbs Ensemble Calculations with an Equation of State: An Application to Vapor-Liquid Equilibria

Abstract

A new modification of the Gibbs ensemble Monte Carlo computer simulation method for fluid phase equilibria is described. The modification is based on a thermodynamic model for the vapor phase, and uses an equation of state to account for the weak interactions between the vapor phase molecules. Reductions in the computational time by 30–40% as compared to the original Gibbs ensemble method are obtained. The algorithm is applied to Lennard-Jones - (12,6) fluids and their mixtures and the results are in good agreement with results obtained from simulations using the full Gibbs ensemble method.     

Exploring the Interaction of Some N- Benzyloxycarbonyl-L-Phenyl Alanyl-L-Alanine Ketones and Bovine Spleen Cathepsin B by Molecular Modeling and Binding Free Energy Calculation

Abstract

A semi-empirical method for estimation of binding free energy, recently proposed by Aqvist and coworkers, has been effectively tested in several protein-ligand binding cases. We have applied this linear interaction energy method to predict the binding of some N-benzy- loxycarbonyl-L-phenyl alanyl-L-alanine ketones with bovine cathepsin B and computed the respective absolute binding constants from averages of molecular dynamics simulations. It is found that the computer simulation results agree well with available experimental data and make it possible to understand better the origin of tight binding and inhibitor specificity of cathepsin B.