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At least 1,243 records · Page 69Linked to original sources
PubMed2001

Large vortex-like structure of dipole field in computer models of liquid water and dipole-bridge between biomolecules.

We propose a framework to describe the cooperative orientational motions of water molecules in liquid water and around solute molecules in water solutions. From molecular dynamics (MD) simulation a new quantity "site-dipole field" is defined as the averaged orientation of water molecules that pass through each spatial position. In the site-dipole field of bulk water we found large vortex-like structures of more than 10 A in size. Such coherent patterns persist more than 300 ps although the orientational memory of individual molecules is quickly lost. A 1-ns MD simulation of systems consisting of two amino acids shows that the fluctuations of site-dipole field of solvent are pinned around the amino acids, resulting in a stable dipole-bridge between side-chains of amino acids. The dipole-bridge is significantly formed even for the side-chain separation of 14 A, which corresponds to five layers of water. The way that dipole-bridge forms sensitively depends on the side-chain orientations and thereby explains the specificity in the solvent-mediated interactions between biomolecules.

Amino Acids↗
PubMed2000

Computational models of temporal processing in the auditory thalamus.

Previous work has shown that neurons in the medial geniculate body (MGB) of the echolocating bat, Myotis lucifugus, display response properties that are distinguishable from those of their afferents in the inferior colliculus (IC). Specifically, MGB neurons display phasic temporal discharge patterns, poor entrainment to trains of constant-amplitude sound pulses, and facilitated responses to amplitude-modulated trains of sound pulses (Llano and Feng 1999). In this study we used a modeling approach to examine the relative contributions of different known sources of inhibition on the temporal response properties of auditory thalamocortical neurons. We found that GABA(A)-mediated post-excitatory inhibition resulting from coactivation of thalamocortical neurons and local inhibitory interneurons (in a triadic arrangement) is sufficient to reproduce many of the temporal response properties of MGB neurons. Addition of long-duration GABA(B)-mediated inhibition gave the thalamocortical neuron temporal response characteristics that more closely resemble those seen in the experimental data. Neither recurrent inhibition from the thalamic reticular nucleus nor postsynaptic nonlinear mechanisms were necessary to reproduce the temporal transformations between the IC and MGB. This work suggests that feed-forward inhibitory circuitry, coupled with slow GABA(B)-mediated inhibition, can emulate temporal information processing at the MGB. The transformation taking place in the MGB can be used to extract salient features from complex, time-varying stimuli, such as echoes returning from moving prey.

Animals↗
PubMed2004

Resrad-recycle: a computer model for analyzing radiation exposures resulting from recycling radioactively contaminated scrap metals or reusing radioactively surface-contaminated materials and equipment.

RESRAD-RECYCLE is a computer code designed by Argonne National Laboratory (ANL) to be used in making decisions about the disposition of radioactively contaminated materials and scrap metals. It implements a pathway analysis methodology to evaluate potential radiation exposures resulting from the recycling of contaminated scrap metals and the reuse of surface-contaminated materials and equipment. For modeling purposes, it divides the entire metal recycling process into six steps: (1) scrap delivery, (2) scrap melting, (3) ingot delivery, (4) product fabrication, (5) product distribution, and (6) use of finished product. RESRAD-RECYCLE considers the reuse of surface-contaminated materials in their original forms. It contains representative exposure scenarios for each recycling step and the reuse process; users can also specify scenarios if desired. The model calculates individual and collective population doses for workers involved in the recycling process and for the public using the finished products. The results are then used to derive clearance levels for the contaminated materials on the basis of input dose restrictions. The model accounts for radiological decay and ingrowth, dilution and partitioning during melting, and distribution of refined metal in the various finished products, as well as the varying densities and geometries of the radiation sources during the recycling process. A complete material balance in terms of mass and radioactivity during the recycling process can also be implemented. In an international validation study, the radiation doses calculated by RESRAD-RECYCLE were shown to agree fairly well with actual measurement data.

Body Burden↗
PubMedDate not supplied

Noise-induced impulse pattern modifications at different dynamical period-one situations in a computer model of temperature encoding.

We used a minimal Hodgkin-Huxley type model of cold receptor discharges to examine how noise interferes with the non-linear dynamics of the ionic mechanisms of neuronal stimulus encoding. The model is based on the assumption that spike-generation depends on subthreshold oscillations. With physiologically plausible temperature scaling, it passes through different impulse patterns which, with addition of noise, are in excellent agreement with real experimental data. The interval distributions of purely deterministic simulations, however, exhibit considerable differences compared to the noisy simulations especially at the bifurcations of deterministically period-one discharges. We, therefore, analyzed the effects of noise in different situations of deterministically regular period-one discharges: (1) at high-temperatures near the transition to subthreshold oscillations and to burst discharges, and (2) at low-temperatures close to and more far away from the bifurcations to chaotic dynamics. The data suggest that addition of noise can considerably extend the dynamical behavior of the system with coexistence of different dynamical situations at deterministically fixed parameter constellations. Apart from well-described coexistence of spike-generating and subthreshold oscillations also mixtures of tonic and bursting patterns can be seen and even transitions to unstable period-one orbits seem to appear. The data indicate that cooperative effects between low- and high-dimensional dynamics have to be considered as qualitatively important factors in neuronal encoding.

Computer Simulation↗
PubMed2006

Structural and functional characterization of human microsomal prostaglandin E synthase-1 by computational modeling and site-directed mutagenesis.

Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) has recently been recognized as a novel, promising drug target for inflammation-related diseases. Functional and pathological studies on this enzyme further stimulate to understand its structure and the structure-function relationships. Using an approach of the combined structure prediction, molecular docking, site-directed mutagenesis, and enzymatic activity assay, we have developed the first three-dimensional (3D) model of the substrate-binding domain (SBD) of mPGES-1 and its binding with substrates prostaglandin H2 (PGH2) and glutathione (GSH). In light of the 3D model, key amino acid residues have been identified for the substrate binding and the obtained experimental activity data have confirmed the computationally determined substrate-enzyme binding mode. Both the computational and experimental results show that Y130 plays a vital role in the binding with PGH2 and, probably, in the catalytic reaction process. R110 and T114 interact intensively with the carboxyl tail of PGH2, whereas Q36 and Q134 only enhance the PGH2-binding affinity. The modeled binding structure indicates that substrate PGH2 interacts with GSH through hydrogen binding between the peroxy group of PGH2 and the -SH group of GSH. The -SH group of GSH is expected to attack the peroxy group of PGH2, initializing the catalytic reaction transforming PGH2 to prostaglandin E2 (PGE2). The overall agreement between the calculated and experimental results demonstrates that the predicted 3D model could be valuable in future rational design of potent inhibitors of mPGES-1 as the next-generation inflammation-related therapeutic.

Algorithms↗
PubMed2002

The effects of ventilation pattern on carbon dioxide transfer in three computer models of the airways.

We investigate the effects on arterial P(CO(2)) and on arterial-end tidal P(CO(2)) difference of six different ventilation patterns of equal tidal volume, and also of various combinations of tidal volume and respiratory rate that maintain a constant alveolar ventilation. We use predictions from three different mathematical models. Models 1 (distributed) and 2 (compartmental) include combined convection and diffusion effects. Model 3 incorporates a single well-mixed alveolar compartment and an anatomical dead-space in which plug flow occurs. We found that: (i) breathing patterns with longer inspiratory times yield lower arterial P(CO(2)); (ii) varying tidal volume and respiratory rate so that alveolar ventilation is kept constant may change both PA(CO(2)) and the PA(CO(2))-PET(CO(2)) difference; (iii) the distributed model predicts higher end-tidal and arterial P(CO(2)) than the compartmental models under similar conditions; and (iv) P(CO(2)) capnograms predicted by the distributed model exhibit longer phase I and steeper phase II than other models.

Animals↗
PubMed1976

A computer model allowing maintenance of large amounts of genetic variability in Mendelian populations. II. The balance of forces between linkage and random assortment.

It is shown, through theory and computer simulations of outbreeding Mendelian populations, that there may be conditions under which a balance is struck between two facotrs. The first is the advantage of random assortment, which will, when multilocus selection is for intermediate equilibrium values, lead to higher average heterozygosity than when linkage is introduced. There is some indication that random assortment is also advantageous when selection is toward a uniform distribution of equilibrium values. The second factor is the advantage of linkage between loci having positive epistatic interactions. When multilocus selection is for a bimodal distribution of equilibrium values an early advantage of random assortment is replaced by a later disadvantage. Linkage disequilibrium, which in finite populations is increased only by random or selective sampling, may hinder the movement of alleles to their selective equilibria, thus leading to the advantage of random assortment.-Some consequences of this approach to the structure of natural populations are discussed.

Computers↗