70 research outputs found
Density of States Monte Carlo Method for Simulation of Fluids
A Monte Carlo method based on a density-of-states sampling is proposed for
study of arbitrary statistical mechanical ensembles in a continuum. A random
walk in the two-dimensional space of particle number and energy is used to
estimate the density of states of the system; this density of states is
continuously updated as the random walk visits individual states. The validity
and usefulness of the method are demonstrated by applying it to the simulation
of a Lennard-Jones fluid. Results for its thermodynamic properties, including
the vapor-liquid phase coexistence curve, are shown to be in good agreement
with high-accuracy literature data.Comment: 5 pages, 3 figures, accepted by J Chem Phy
Multicanonical Parallel Tempering
We present a novel implementation of the parallel tempering Monte Carlo
method in a multicanonical ensemble. Multicanonical weights are derived by a
self-consistent iterative process using a Boltzmann inversion of global energy
histograms. This procedure gives rise to a much broader overlap of
thermodynamic-property histograms; fewer replicas are necessary in parallel
tempering simulations, and the acceptance of trial swap moves can be made
arbitrarily high. We demonstrate the usefulness of the method in the context of
a grand-multicanonical ensemble, where we use multicanonical simulations in
energy space with the addition of an unmodified chemical potential term in
particle-number space. Several possible implementations are discussed, and the
best choice is presented in the context of the liquid-gas phase transition of
the Lennard-Jones fluid. A substantial decrease in the necessary number of
replicas can be achieved through the proposed method, thereby providing a
higher efficiency and the possibility of parallelization.Comment: 8 pages, 3 figure, accepted by J Chem Phy
Hyperparallel tempering Monte Carlo simulation of polymeric systems
This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder
Hypoxia Inactivates the VHL Tumor Suppressor through PIASy-Mediated SUMO Modification
The hypoxic microenvironment contributes to embryonic development and tumor progression through stabilization of the potent transcriptional factor HIFα. In normoxia, the tumor suppressor protein VHL acts as an E3 ubiquitin ligase to target HIFα for proteolytic destruction. Increasing evidence shows that VHL is a multifunctional adaptor involved in inhibition of HIFα-dependent and independent cellular processes. However, the molecular effect of hypoxic stress on VHL functions remains elusive. Here we report that PIASy, a SUMO E3 ligase upregulated in hypoxia, interacts with VHL and induces VHL SUMOylation on lysine residue 171. Moreover, PIASy-mediated SUMO1 modification induces VHL oligomerization and abrogates its inhibitory function on tumor cell growth, migration and clonogenicity. Knockdown of PIASy by small interfering RNA leads to reduction of VHL oligomerization and increases HIF1α degradation. These findings reveal a unique molecular strategy for inactivation of VHL under hypoxic stress
Molecular dynamics simulation of discontinuous volume phase transitions in highly-charged crosslinked polyelectrolyte networks with explicit counterions in good solvent
Epstein-Barr Virus Nuclear Antigen 3C Facilitates G1-S Transition by Stabilizing and Enhancing the Function of Cyclin D1
EBNA3C, one of the Epstein-Barr virus (EBV)-encoded latent antigens, is essential for primary B-cell transformation. Cyclin D1, a key regulator of G1 to S phase progression, is tightly associated and aberrantly expressed in numerous human cancers. Previously, EBNA3C was shown to bind to Cyclin D1 in vitro along with Cyclin A and Cyclin E. In the present study, we provide evidence which demonstrates that EBNA3C forms a complex with Cyclin D1 in human cells. Detailed mapping experiments show that a small N-terminal region which lies between amino acids 130–160 of EBNA3C binds to two different sites of Cyclin D1- the N-terminal pRb binding domain (residues 1–50), and C-terminal domain (residues 171–240), known to regulate Cyclin D1 stability. Cyclin D1 is short-lived and ubiquitin-mediated proteasomal degradation has been targeted as a means of therapeutic intervention. Here, we show that EBNA3C stabilizes Cyclin D1 through inhibition of its poly-ubiquitination, and also increases its nuclear localization by blocking GSK3β activity. We further show that EBNA3C enhances the kinase activity of Cyclin D1/CDK6 which enables subsequent ubiquitination and degradation of pRb. EBNA3C together with Cyclin D1-CDK6 complex also efficiently nullifies the inhibitory effect of pRb on cell growth. Moreover, an sh-RNA based strategy for knock-down of both cyclin D1 and EBNA3C genes in EBV transformed lymphoblastoid cell lines (LCLs) shows a significant reduction in cell-growth. Based on these results, we propose that EBNA3C can stabilize as well as enhance the functional activity of Cyclin D1 thereby facilitating the G1-S transition in EBV transformed lymphoblastoid cell lines
Hyper-parallel tempering Monte Carlo: Application to the Lennard-Jones fluid and the restricted primitive model
This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder
Effects of charge, size, and shape-asymmetry on the phase behavior of model electrolytes
This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder
Hyperparallel tempering Monte Carlo simulation of polymeric systems
This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder
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