15,832 research outputs found
Absolute FKBP binding affinities obtained via non-equilibrium unbinding simulations
We compute absolute binding affinities for two ligands bound to the FKBP
protein using non-equilibrium unbinding simulations. The methodology is
straight-forward, requiring little or no modification to many modern molecular
simulation packages. The approach makes use of a physical pathway, eliminating
the need for complicated alchemical decoupling schemes. Results of this study
are promising. For the ligands studied here the binding affinities are
typically estimated within less than 4.0 kJ/mol of the target values; and the
target values are within less than 1.0 kJ/mol of experiment. These results
suggest that non-equilibrium simulation could provide a simple and robust means
to estimate protein-ligand binding affinities.Comment: 9 pages, 3 figures (no necessary color). Changes made to methodology
and results between revision
Exact solution of a model DNA-inversion genetic switch with orientational control
DNA inversion is an important mechanism by which bacteria and bacteriophage
switch reversibly between phenotypic states. In such switches, the orientation
of a short DNA element is flipped by a site-specific recombinase enzyme. We
propose a simple model for a DNA inversion switch in which recombinase
production is dependent on the switch state (orientational control). Our model
is inspired by the fim switch in Escherichia coli. We present an exact
analytical solution of the chemical master equation for the model switch, as
well as stochastic simulations. Orientational control causes the switch to
deviate from Poissonian behaviour: the distribution of times in the on state
shows a peak and successive flip times are correlated.Comment: Revised version, accepted for publicatio
Manifestation of nonequilibrium initial conditions in molecular rotation: the generalized J-diffusion model
In order to adequately describe molecular rotation far from equilibrium, we
have generalized the J-diffusion model by allowing the rotational relaxation
rate to be angular momentum dependent. The calculated nonequilibrium rotational
correlation functions (CFs) are shown to decay much slower than their
equilibrium counterparts, and orientational CFs of hot molecules exhibit
coherent behavior, which persists for several rotational periods. As distinct
from the results of standard theories, rotational and orientational CFs are
found to dependent strongly on the nonequilibrium preparation of the molecular
ensemble. We predict the Arrhenius energy dependence of rotational relaxation
times and violation of the Hubbard relations for orientational relaxation
times. The standard and generalized J-diffusion models are shown to be almost
indistinguishable under equilibrium conditions. Far from equilibrium, their
predictions may differ dramatically
The \u3ci\u3ePhycodnaviridae\u3c/i\u3e: The Story of How Tiny Giants Rule the World
The family Phycodnaviridae encompasses a diverse and rapidly expanding collection of large icosahedral, dsDNA viruses that infect algae. These lytic and lysogenic viruses have genomes ranging from 160 to 560 kb. The family consists of six genera based initially on host range and supported by sequence comparisons. The family is monophyletic with branches for each genus, but the phycodnaviruses have evolutionary roots that connect them with several other families of large DNA viruses, referred to as the nucleocytoplasmic large DNA viruses (NCLDV).The phycodnaviruses have diverse genome structures, some with large regions of noncoding sequence and others with regions of ssDNA. The genomes of members in three genera in the Phycodnaviridae have been sequenced. The genome analyses have revealed more than 1000 unique genes, with only 14 homologous genes in common among the three genera of phycodnaviruses sequenced to date. Thus, their gene diversity far exceeds the number of so-called core genes. Not much is known about the replication of these viruses, but the consequences of these infections on phytoplankton have global affects, including influencing geochemical cycling and weather patterns
The \u3ci\u3ePhycodnaviridae\u3c/i\u3e: The Story of How Tiny Giants Rule the World
The family Phycodnaviridae encompasses a diverse and rapidly expanding collection of large icosahedral, dsDNA viruses that infect algae. These lytic and lysogenic viruses have genomes ranging from 160 to 560 kb. The family consists of six genera based initially on host range and supported by sequence comparisons. The family is monophyletic with branches for each genus, but the phycodnaviruses have evolutionary roots that connect them with several other families of large DNA viruses, referred to as the nucleocytoplasmic large DNA viruses (NCLDV).The phycodnaviruses have diverse genome structures, some with large regions of noncoding sequence and others with regions of ssDNA. The genomes of members in three genera in the Phycodnaviridae have been sequenced. The genome analyses have revealed more than 1000 unique genes, with only 14 homologous genes in common among the three genera of phycodnaviruses sequenced to date. Thus, their gene diversity far exceeds the number of so-called core genes. Not much is known about the replication of these viruses, but the consequences of these infections on phytoplankton have global affects, including influencing geochemical cycling and weather patterns
Efficient Reactive Brownian Dynamics
We develop a Split Reactive Brownian Dynamics (SRBD) algorithm for particle
simulations of reaction-diffusion systems based on the Doi or volume reactivity
model, in which pairs of particles react with a specified Poisson rate if they
are closer than a chosen reactive distance. In our Doi model, we ensure that
the microscopic reaction rules for various association and disassociation
reactions are consistent with detailed balance (time reversibility) at
thermodynamic equilibrium. The SRBD algorithm uses Strang splitting in time to
separate reaction and diffusion, and solves both the diffusion-only and
reaction-only subproblems exactly, even at high packing densities. To
efficiently process reactions without uncontrolled approximations, SRBD employs
an event-driven algorithm that processes reactions in a time-ordered sequence
over the duration of the time step. A grid of cells with size larger than all
of the reactive distances is used to schedule and process the reactions, but
unlike traditional grid-based methods such as Reaction-Diffusion Master
Equation (RDME) algorithms, the results of SRBD are statistically independent
of the size of the grid used to accelerate the processing of reactions. We use
the SRBD algorithm to compute the effective macroscopic reaction rate for both
reaction- and diffusion-limited irreversible association in three dimensions.
We also study long-time tails in the time correlation functions for reversible
association at thermodynamic equilibrium. Finally, we compare different
particle and continuum methods on a model exhibiting a Turing-like instability
and pattern formation. We find that for models in which particles diffuse off
lattice, such as the Doi model, reactions lead to a spurious enhancement of the
effective diffusion coefficients.Comment: To appear in J. Chem. Phy
Mesoscopic simulations of the counterion-induced electroosmotic flow - a comparative study
We present mesoscopic simulations of the counterion-induced electroosmotic
flow in different electrostatic coupling regimes. Two simulation methods are
compared, Dissipative Particle Dynamics (DPD) and coupled
Lattice-Boltzmann/Molecular Dynamics (LB/MD). A general mapping scheme to match
DPD to LB/MD is developed. For the weak-coupling regime, analytic expressions
for the flow profiles in the presence of partial-slip as well as no-slip
boundary conditions are derived from the Poisson-Boltzmann and Stokes
equations, which are in good agreement with the numerical results. The
influence of electrofriction and partial slip on the flow profiles is
discussed.Comment: 10 pages, 8 figures, 3 tables, additional references and minor
changes in the tex
Main phase transition in lipid bilayers: phase coexistence and line tension in a soft, solvent-free, coarse-grained model
We devise a soft, solvent-free, coarse-grained model for lipid bilayer
membranes. The non-bonded interactions take the form of a weighted-density
functional which allows us to describe the thermodynamics of self-assembly and
packing effects of the coarse-grained beads in terms of a density expansion of
the equation of state and the weighting functions that regularize the
microscopic bead densities, respectively. Identifying the length and energy
scales via the bilayer thickness and the thermal energy scale, kT, the model
qualitatively reproduces key characteristics (e.g., bending rigidity, area per
lipid molecules, and compressibility) of lipid membranes. We employ this model
to study the main phase transition between the liquid and the gel phase of the
bilayer membrane. We accurately locate the phase coexistence using free energy
calculations and also obtain estimates for the bare and the thermodynamic line
tension.Comment: 21 pages, 12 figures. Submitted to J. Chem. Phy
High-z radio starbursts host obscured X-ray AGN
We use Virtual Observatory methods to investigate the association between
radio and X-ray emission at high redshifts. Fifty-five of the 92 HDF(N) sources
resolved by combining
MERLIN+VLA data were detected by Chandra, of which 18 are hard enough and
bright enough to be obscured AGN. The high-z population of microJy radio
sources is dominated by starbursts an order of magnitude more active and more
extended than any found at z<1 and at least a quarter of these simultaneously
host highly X-ray-luminous obscured AGN.Comment: 4 pages, 2 figures, To appear in the proceedings of 'At the Edge of
the Universe' (9-13 October 2006, Sintra, Portugal
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