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Find video protocols related to scientific articles indexed in Pubmed.
Calibrated Langevin-dynamics simulations of intrinsically disordered proteins.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 10-13-2014
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We perform extensive coarse-grained (CG) Langevin dynamics simulations of intrinsically disordered proteins (IDPs), which possess fluctuating conformational statistics between that for excluded volume random walks and collapsed globules. Our CG model includes repulsive steric, attractive hydrophobic, and electrostatic interactions between residues and is calibrated to a large collection of single-molecule fluorescence resonance energy transfer data on the interresidue separations for 36 pairs of residues in five IDPs: ?-, ?-, and ?-synuclein, the microtubule-associated protein ?, and prothymosin ?. We find that our CG model is able to recapitulate the average interresidue separations regardless of the choice of the hydrophobicity scale, which shows that our calibrated model can robustly capture the conformational dynamics of IDPs. We then employ our model to study the scaling of the radius of gyration with chemical distance in 11 known IDPs. We identify a strong correlation between the distance to the dividing line between folded proteins and IDPs in the mean charge and hydrophobicity space and the scaling exponent of the radius of gyration with chemical distance along the protein.
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Connection between the packing efficiency of binary hard spheres and the glass-forming ability of bulk metallic glasses.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 09-29-2014
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We perform molecular dynamics simulations to compress binary hard spheres into jammed packings as a function of the compression rate R, size ratio ?, and number fraction x_{S} of small particles to determine the connection between the glass-forming ability (GFA) and packing efficiency in bulk metallic glasses (BMGs). We define the GFA by measuring the critical compression rate R_{c}, below which jammed hard-sphere packings begin to form "random crystal" structures with defects. We find that for systems with ??0.8 that do not demix, R_{c} decreases strongly with ??_{J}, as R_{c}?exp(-1/??_{J}^{2}), where ??_{J} is the difference between the average packing fraction of the amorphous packings and random crystal structures at R_{c}. Systems with ??0.8 partially demix, which promotes crystallization, but we still find a strong correlation between R_{c} and ??_{J}. We show that known metal-metal BMGs occur in the regions of the ? and x_{S} parameter space with the lowest values of R_{c} for binary hard spheres. Our results emphasize that maximizing GFA in binary systems involves two competing effects: minimizing ? to increase packing efficiency, while maximizing ? to prevent demixing.
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Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses.
Cell Host Microbe
PUBLISHED: 02-11-2013
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Death receptors (DRs) of the TNFR superfamily contribute to antiviral immunity by promoting apoptosis and regulating immune homeostasis during infection, and viral inhibition of DR signaling can alter immune defenses. Here we identify the human cytomegalovirus (HCMV) UL141 glycoprotein as necessary and sufficient to restrict TRAIL DR function. Despite showing no primary sequence homology to TNF family cytokines, UL141 binds the ectodomains of both human TRAIL DRs with affinities comparable to the natural ligand TRAIL. UL141 binding promotes intracellular retention of the DRs, thus protecting virus infected cells from TRAIL and TRAIL-dependent NK cell-mediated killing. The identification of UL141 as a herpesvirus modulator of the TRAIL DRs strongly implicates this pathway as a regulator of host defense to HCMV and highlights UL141 as a pleiotropic inhibitor of NK cell effector function.
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Molecular simulations of the fluctuating conformational dynamics of intrinsically disordered proteins.
Phys Rev E Stat Nonlin Soft Matter Phys
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Intrinsically disordered proteins (IDPs) do not possess well-defined three-dimensional structures in solution under physiological conditions. We develop all-atom, united-atom, and coarse-grained Langevin dynamics simulations for the IDP ?-synuclein that include geometric, attractive hydrophobic, and screened electrostatic interactions and are calibrated to the inter-residue separations measured in recent single-molecule fluorescence energy transfer (smFRET) experiments. We find that ?-synuclein is disordered, with conformational statistics that are intermediate between random walk and collapsed globule behavior. An advantage of calibrated molecular simulations over constraint methods is that physical forces act on all residues, not only on residue pairs that are monitored experimentally, and these simulations can be used to study oligomerization and aggregation of multiple ?-synuclein proteins that may precede amyloid formation.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.