238 research outputs found
Finite Size Polyelectrolyte Bundles at Thermodynamic Equilibrium
We present the results of extensive computer simulations performed on
solutions of monodisperse charged rod-like polyelectrolytes in the presence of
trivalent counterions. To overcome energy barriers we used a combination of
parallel tempering and hybrid Monte Carlo techniques. Our results show that for
small values of the electrostatic interaction the solution mostly consists of
dispersed single rods. The potential of mean force between the polyelectrolyte
monomers yields an attractive interaction at short distances. For a range of
larger values of the Bjerrum length, we find finite size polyelectrolyte
bundles at thermodynamic equilibrium. Further increase of the Bjerrum length
eventually leads to phase separation and precipitation. We discuss the origin
of the observed thermodynamic stability of the finite size aggregates
Polyelectrolyte Bundles
Using extensive Molecular Dynamics simulations we study the behavior of
polyelectrolytes with hydrophobic side chains, which are known to form
cylindrical micelles in aqueous solution. We investigate the stability of such
bundles with respect to hydrophobicity, the strength of the electrostatic
interaction, and the bundle size. We show that for the parameter range relevant
for sulfonated poly-para-phenylenes (PPP) one finds a stable finite bundle
size. In a more generic model we also show the influence of the length of the
precursor oligomer on the stability of the bundles. We also point out that our
model has close similarities to DNA solutions with added condensing agents,
hinting to the possibility that the size of DNA aggregates is under certain
circumstances thermodynamically limited.Comment: 10 pages, 8 figure
Semi-classical buckling of stiff polymers
A quantitative theory of the buckling of a worm like chain based on a
semi-classical approximation of the partition function is presented. The
contribution of thermal fluctuations to the force-extension relation that
allows to go beyond the classical Euler buckling is derived in the linear and
non-linear regime as well. It is shown that the thermal fluctuations in the
nonlinear buckling regime increase the end-to-end distance of the semiflexible
rod if it is confined to 2 dimensions as opposed to the 3 dimensional case. Our
approach allows a complete physical understanding of buckling in D=2 and in D=3
below and above the Euler transition.Comment: Revtex, 17 pages, 4 figure
Pharmacokinetic/pharmacodynamic modeling of the antinociceptive effects of (+)-tramadol in the rat: role of cytochrome P450 2D activity
In this study the role of cytochrome P450 2D (CYP2D) in the pharmacokinetic/pharmacodynamic relationship of (+)-tramadol [(+)-T] has been explored in rats. Male Wistar rats were infused with (+)-T in the absence of and during pretreatment with a reversible CYP2D inhibitor quinine (Q), determining plasma concentrations of Q, (+)-T, and (+)-O-demethyltramadol [(+)-M1], and measuring antinociception. Pharmacokinetics of (+)-M1, but not (+)-T, was affected by Q pretreatment: early after the start of (+)-T infusion, levels of (+)-M1 were significantly lower (P < 0.05). However, at later times during Q infusion those levels increased continuously, exceeding the values found in animals that did not receive the inhibitor. These results suggest that CYP2D is involved in the formation and elimination of (+)-M1. In fact, results from another experiment where (+)-M1 was given in the presence and in absence of Q showed that (+)-M1 elimination clearance (CL(ME0)) was significantly lower (P < 0.05) in animals receiving Q. Inhibition of both (+)-M1 formation clearance (CL(M10)) and CL(ME0) were modeled by an inhibitory E(MAX) model, and the estimates (relative standard error) of the maximum degree of inhibition (E(MAX)) and IC(50), plasma concentration of Q eliciting half of E(MAX) for CL(M10) and CL(ME0), were 0.94 (0.04), 97 (0.51) ng/ml, and 48 (0.42) ng/ml, respectively. The modeling of the time course of antinociception showed that the contribution of (+)-T was negligible and (+)-M1 was responsible for the observed effects, which depend linearly on (+)-M1 effect site concentrations. Therefore, the CYP2D activity is a major determinant of the antinociception elicited after (+)-T administration
Nucleotide Binding Switches the Information Flow in Ras GTPases
The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (SGDP and SGTP, respectively). For all the considered systems, the intrinsic flexibility of SGDP was higher than that of SGTP, suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, SGDP of Gαt, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP
- …