Axial Distribution Function Research Articles

Blocking the catalytic mechanism of MurC ligase enzyme from Acinetobacter baumannii: An in Silico guided study towards the discovery of natural antibiotics

Acinetobacter baumannii belongs to the most critical group of bacterial pathogens that are resistant to large number of antibiotics, including the highly effective carbapenems and third generation cephalosporins. Novel antibiotics targeting unique pathways of the said pathogen could reduce the mortality rate due to its infections that are impervious to the current antibiotics. Herein, we explored a library of natural compounds that was filtered first for drug-like, followed by lead-like molecules, which were finally utilized in structure based virtual screening to identify the most promising inhibitor for the Ligand binding (LB) domain of MurC ligase enzyme. The inhibitor (1′-((2H-imidazol-2-yl)methyl)-N-(pyridin-2-yl)-1′,2′-dihydro-[4,4′-bipyridin]-2-amine) was observed with a conformation to target most conserved and catalytically critical residues of both the intended LB as well as the ATP binding domain of MurC. This multi-domain inhibitor revealed to have an excellent pharmacokinetics profile thus likely to have safe and effective therapeutic applications for the future. Molecular dynamics simulation in aqueous solution further supported the high affinity of the compound for the target site involving strong hydrogen bonding. At residue level, radial distribution function (RDF) and axial distribution function (AFD) illustrated Asp334 as the most critical amino acid that drives recognition, binding, and activity of the compound. The complex stability was validated by subjecting it to Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA), Molecular Mechanics Generalized Born Surface Area (MMGBSA) and WaterSwap based binding free energy calculations. The system was observed with high stability: total binding energy in MMGBSA (−48.45 kcal/mol) and MMPBSA (−3.62 kcal/mol). The columbic interactions were noticed to dominate (−336.90 kcal/mol), followed by van der Waals energies (−45.52 kcal/mol) in MurC-inhibitor binding. The absolute binding free energy estimated by WaterSwap was −43.2 kcal/mol, depicting higher complex stability. The screened scaffold might be used in functional groups substitution to achieve further lead optimization.

Can We Describe Graphene Confined Water Structures as Overlapping of Approaching Graphene–Water Interfacial Structures?

We investigate the microscopic mechanisms of the overlap of interfacial structures in confined fluids and attempt to answer the question whether the confined structures can be predicted from the original density profiles of individual solid–fluid interfaces. For that purpose, we perform (globally) isobaric–isothermal (locally, grand canonical) molecular dynamics simulations to extract not only the axial distribution functions of the water sites for the uncoupled graphene–water interfaces, but also those corresponding to the confined aqueous environments over the interplate range 8 ≤ h (Å) ≤ 28 typically at ambient conditions. We have tested two (i.e., an arithmetic and a geometric) superposition approximations for the singlet density of confined water between flat graphene plates, as well as for a combination of flat and corrugated graphene plates. The outcome of this study suggests that the answer to the title’s question is a “yes”, provided that the interplate distance h is large enough to avoid fluid geometric packing frustration.

Water Flow in Carbon Nanotubes: Transition to Subcontinuum Transport

The structure and flow of water inside 75 and 150 nm-long carbon nanotubes with diameters ranging from 0.83 to 1.66 nm are examined using molecular dynamics simulation. The flow rate enhancement, defined as the ratio of the observed flow rate to that predicted from the no-slip Poiseuille relation, is calculated for each tube and the liquid structure is examined using an axial distribution function. The relationship between the intermolecular water structure and water flow is quantified and differences between continuum and subcontinuum flow are discussed.

Structure and rheological behavior of highly charged colloidal particles in a cylindrical pore I. Effect of pore size

In this work we performed nonequilibrium Brownian dynamics (NEBD) computer simulations of highly charged colloidal particles in diluted suspension under a parabolic flow in cylindrical pores. The influence of charged and neutral cylindrical pores on the structure and rheology of suspensions is analyzed. A shear-induced disorder–order–disorder-like transition was monitored for low shear rates and small pore diameters. We calculate the concentration profiles, axial distribution functions, and axial–angular pair correlation functions to determine the structural properties at steady state for a constant shear flow for different pore sizes and flow strengths. Similar behavior has been observed in a planar narrow channel in the case of charged interacting colloidal particles (M.A. Valdez, O. Manero, J. Colloid Interface Sci. 190 (1997) 81). The mobility of the particles in the radial direction decreases rapidly with the flow and becomes practically frozen. The flow exhibits non-Newtonian shear thinning behavior due to interparticle interactions and particle–wall interaction; the apparent viscosity is lower as the pore diameter decreases, giving rise to an apparent slip in the colloidal suspension. The calculated slip velocity was higher than that obtained in a rectangular slit under shear flow.

Residence-time distributions for chaotic flows in pipes.

In this paper we derive two rigorous properties of residence-time distributions for flows in pipes and mixers motivated by computational results of Khakhar et al. [Chem. Eng. Sci. 42, 2909 (1987)], using some concepts from ergodic theory. First, a curious similarity between the isoresidence-time plots and Poincare maps of the flow observed in Khakhar et al. is resolved. It is shown that in long pipes and mixers, Poincare maps can serve as a useful guide in the analysis of isoresidence-time plots, but the two are not equivalent. In particular, for long devices isoresidence-time sets are composed of orbits of the Poincare map, but each isoresidence-time set can be comprised of many orbits. Second, we explain the origin of multimodal residence-time distributions for nondiffusive motion of particles in pipes and mixers. It is shown that chaotic regions in the Poincare map contribute peaks to the appropriately defined and rescaled axial distribution functions. (c) 1999 American Institute of Physics.

Quantitative modeling of the anisotropy of ultrasonic backscatter from canine myocardium

Reports extensions and new results of the First Time Domain Born approximation model used by Mottley and Miller (1982) to describe the anisotropy of ultrasonic backscatter measured in canine myocardium. The interaction of an ultrasonic plane wave impulse with a single cylindrical scatterer using time and frequency domain approaches is reviewed. Myocardial tissue is modeled as a suspension of aligned cylindrically shaped scatterers uniformly distributed in a homogeneous medium. The authors propose extensions to this model to deal with nonideal scatterer orientation, by introducing axial distribution functions and scatterer size distributions based on histology, modeled as a uniform distribution. The backscatter coefficient in the range 2.0-8.0 MHz is calculated. An algorithm to compute the average differential scattering cross section is presented. Ultrasonic elastic properties of myocardial tissue are discussed. Results of the anisotropy of the numerically computed backscatter parameters for model media having nominal mechanical and acoustic properties of canine myocardial tissue are presented and compared to available experimental data along with discussion of possible conclusions. >

The Boltzmann-Vlasov Equation in Or hogonal Curvilinear Coodinate System and its Application in Non-Uniform Magnetic Field

We have, derived the simple form of Boltzmann-Vlasov equation in the orthogonal curvilinear coodinate system by use of the curvature and the tortion of the coodinate axes, tried to introduce a term of the effect of non-uniform magnetic field configuration and formulated it also in a simple magnetic mirror field configuration. Moreover we have dirived a few of momentum equations from the Boltzmann-Vlasov. equation derived above. it is shown that the derived momentum equations become to well-known fluid equations of plasma if fluid approximation is satisfied. In application, we have examined the axial distribution function of collision-free plasma particles in a idealized magnetic mirror field configuration by moo of the Boltzmann-Vlsov equation in nor-uniform magnetic field.