Evidence for a credit-card-swipe mechanism in the human PC floppase ABCB4

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Study on the hydrolysis mechanism of phosphodiesterase 4 using molecular dynamics simulations

We carried out NPT molecular dynamics simulations in an explicit solvent to better understand the mechanism of cyclic adenosine monophosphates (cAMP) hydrolysis by phosphodiesterase 4 (PDE4) enzyme on atomic details and to obtain information on the dynamics characteristic of the catalytic domains of PDE4. In analyzing the water hydrogen-bond network around the active site, we also showed the importance of water in drug–protein interactions. In addition, we reported the characteristics of the hydration pattern and the dynamic distance distribution around the interesting residues. The results indicated that Asp318 plays the role of a general base that can activate water molecule for nucleophilic attack on cAMP. As expected, His160 plays the role of a proton donor for cAMP.     

The mechanism of the converter domain rotation in the recovery stroke of myosin motor protein

Upon ATP binding, myosin motor protein is found in two alternative conformations, prerecovery state M* and postrecovery state M**. The transition from one state to the other, known as the recovery stroke, plays a key role in the myosin functional cycle. Despite much recent research, the microscopic details of this transition remain elusive. A critical step in the recovery stroke is the rotation of the converter domain from “up” position in prerecovery state to “down” position in postrecovery state that leads to the swing of the lever arm attached to it. In this work, we demonstrate that the two rotational states of the converter domain are determined by the interactions within a small structural motif in the force‐generating region of the protein that can be accurately modeled on computers using atomic representation and explicit solvent. Our simulations show that the transition between the two states is controlled by a small helix (SH1) located next to the relay helix and relay loop. A small translation in the position of SH1 away from the relay helix is seen to trigger the transition from “up” state to “down” state. The transition is driven by a cluster of hydrophobic residues I687, F487, and F506 that make significant contributions to the stability of both states. The proposed mechanism agrees well with the available structural and mutational studies. Proteins 2012; © 2012 Wiley Periodicals, Inc.     

Biochemical characterization of activation-associated bovine class I major histocompatibility complex antigens

Summary. Utilizing a 'sandwich' ELISA assay we have been able to demonstrate that mAb W6/32, B1G6 and IL-A19 are reactive with three different monomorphic determinants on bovine class I major histocompatibility complex (MHC) molecules. Sequential immunoprecipitations performed with the mAb revealed that class I molecules on PBM comprise a single population with respect to reactivity with the mAb in that the β2m-associated proteins bear all three epitopes. By contrast, TCGF-driven lymphoblasts and cells transformed by Theileria parva (Tp) additionally express molecules of Mr 45000 bound to β2m which are recognized by mAb B1G6 and IL-A19 but not by W6/32. These two subclasses of molecules were further distinguished on the basis that, when tunicamycin was added to cultures in the preparation of cells for analysis, mAb W6/32 precipitated class I heavy chains of Mr 39000 while the extra molecules detected only by mAb B1G6 and IL-A19 were of Mr 37000 and 39000. On thymocytes, the mAb W6/32-non-reactive class I molecules are present in low amounts and are expressed by cells in the medulla area, unlike BoT1 (analogous to human CD1) molecules which are expressed by the cortical cells. Our studies also revealed that the supposed β2m-specific mAb B1G6 does not recognize the β2m-associated molecules (BoT1) precipitated by mAb TH97A and thus the specificity of mAb B1G6 in cattle is for an epitope on bovine β2m which is strongly influenced by the nature of the heavy chain with which the β2m is associated.     

Direct numerical simulation of expiratory crackles: Relationship between airway closure dynamics and acoustic fluctuations

This paper investigates the relationship between airway closure dynamics and acoustic fluctuations in expiratory crackles using direct numerical simulation. A unified mathematical model is proposed to deal with flow in an airway, elastic deformation of the airway wall, surface tension driven motion of the liquid film that lines the airway, and their acoustic fluctuations because of material compressibility. Airway closure is induced by increasing the surrounding pressure, then the source of the pressure fluctuations is measured over time. Our results show that the airway closure occurs suddenly because of a bridge formation of the liquid film, and high energy transfer occurs between the kinetic energy, the surface energy of the liquid interface, and the elastic energy of the airway wall, invoking a large acoustic fluctuation that causes the expiratory crackles. Nonlinear behavior is observed in terms of the airway wall stiffness; the dynamic motion of the airway closure becomes moderate and both the energy transfer and acoustic fluctuations are dramatically reduced with an increase in airway wall stiffness.     

Molecular dynamics of human alpha-fetoprotein fragment LDSYQCT and its analogs at different dielectric constants

A comparative study of the conformation dynamics of the human alpha-fetoprotein fragment LDSYQCT and heptapeptides derived from it by point substitutions has revealed a significant influence of electrostatic interactions on the set of preferred conformations and dynamics of amino acid residues when the peptides with blocked termini are examined at ? = 1. Peptide flexibility rises when the termini are left free (charged). At ? = 10 or 80, the set of probable conformations for all residues expands to much the same extent, i.e., at higher permittivity of the medium the dynamic effects of amino acid changes are leveled off.     

Evaluating the Feasibility of Eradicating an Invasion

The detectability of invasive organisms influences the costs and benefits of alternative control strategies, and the feasibility of eradicating an infestation. Search theory offers a mathematically rigorous framework for defining and measuring detectability taking account of searcher ability, biological factors and the search environment. In this paper, invasive species detectability is incorporated into a population simulation model. The model is applied to a base set of parameter values that represent reasonable values for a hypothetical weed. The analysis shows the effects of detectability and search effort on the duration of an eradication program. For a given level of detectability and search time, the analysis shows that the variables with the greatest influence on the duration of the eradication effort are search speed, kill efficiency, germination rate and seed longevity. Monte Carlo simulations are performed on a set of four weed scenarios, involving different combinations of plant longevity, seed longevity and plant fecundity. Results of these simulations are presented as probability distributions and allow us to calculate how the probability of eradication will be affected by search strategy.     

Host kairomone learning and foraging success in an egg parasitoid: a simulation model

Abstract 1. Trissolcus basalis (Wollaston) (Hymenoptera: Scelionidae) is an egg parasitoid that recognises chemical residues left by its host the green stink bug Nezara viridula (L.) (Heteroptera: Pentatomidae) as kairomone signals, enabling it to find egg masses in which to lay eggs. 2. Kairomones are usually present as patches deposited by N. viridula females, and recent results (Peri et al., Journal of Experimental Biology, 209 , 3629–3635, 2006) indicated that females of T. basalis are able to learn the features of their foraging environment and to adjust accordingly the amount of time spent on the patches of kairomones they are visiting, depending on whether or not host eggs are found. 3. In order to assess the impact of this learning ability, a Monte Carlo, spatially explicit and individual‐based simulation model was built to quantify the foraging efficiency of T. basalis females in environments with different levels of host abundance and distribution. In all cases, the present study compared the foraging efficiency of simulated T. basalis females having the ability to learn with those lacking this ability. 4. Learning females always visited a higher number of kairomone patches and attacked a higher number of hosts than non‐learning females, especially when there was a high density of kairomone patches in the environment. 5. Learning ability globally appears to allow the maintenance of efficient foraging success, especially when there is a low probability for the kairomone patches to contain discoverable hosts. 6. The increase in foraging efficiency for learning females appears to depend on the characteristics of the habitat in which they are foraging. Results thus suggest that significant variation in learning ability is likely to occur in natural wasp populations facing different environments with different host spatial distributions.     

Female and male Texas cichlids (Herichthys cyanoguttatum) do not fight by the same rules

Selection usually acts differently on males and females duringintrasexual competition for resources and/or mates. Nevertheless,agonistic behavior has been examined both theoretically andempirically mostly in males. Our research questions whethermales and females follow the same rules of engagement in intrasexualcontests as predicted by the sequential assessment model (SAM).The SAM predicts negative correlations between contest intensityand duration and the magnitude of asymmetry in resource holdingpower (RHP) between the contestants, such that the most escalatedcontests are those between similarly endowed individuals. Westaged male and female intrasexual contests with varying degreesof body size asymmetry under a round robin design using themonogamous Texas cichlid fish (Herichthys cyanoguttatum) asa study case. We used Mantel's matrix analysis to compare howthe behavioral content, duration, structure, and outcome ofmale and female contests were affected by the relative bodysize of the contestants. In the case of males, relative sizein each contest predicted outcome, duration, and frequency ofconventional and escalated behaviors according to prevailingtheory. Female contest structure and outcome, however, werenot predicted by the relative size of contestants. We discussour results in terms of other asymmetries that might be importantin structuring female contests, and we propose potential approachesto study female–female aggression.