Search results for "Molecular Dynamic"

showing 10 items of 1090 documents

Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.

2021

The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…

SpliceosomeQH301-705.5Protein ConformationPyridinesRNA SplicingMutantDruggabilityH3B-8800Molecular Dynamics Simulationmedicine.disease_causeCatalysisPiperazinesArticleInorganic ChemistryNeoplasmsspliceosome-mutant cancermedicineHumansPhysical and Theoretical ChemistryBiology (General)Molecular BiologyQD1-999SpectroscopyMutationsplicing modulatorsChemistryOrganic ChemistryWild typeIntronleukemiaGeneral MedicinePhosphoproteinsH3B‐8800molecular dynamicsComputer Science ApplicationsCell biologyChemistryPhenotypeCancer cellRNA splicingMutationRNA Splicing FactorsSpliceosome‐mutant cancerInternational journal of molecular sciences
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Low density lipoproteins and human serum albumin as the carriers of squalenoylated drugs: insights from molecular simulations

2018

We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs accumulate inside the LDL particles. This effect is promoted by the squalene moiety, which acts as an anchor and drives the hydrophilic drugs into the hydrophobic core of the LDL lipid droplet. Our data suggest that LDL particles could be a universal carriers of squalenoylated drugs in the bloodstream. Interaction of gemcitabine-squalene with human serum albumin (HSA) was also studied by ensemble of dockin…

Squalene[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]Drug CompoundingPharmaceutical ScienceSerum Albumin Human02 engineering and technologyPlasma protein bindingMolecular Dynamics Simulation010402 general chemistry01 natural sciencesMolecular Docking SimulationDeoxycytidineSqualenechemistry.chemical_compound[ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]Lipid dropletDrug DiscoverymedicineMoietyHumansComputingMilieux_MISCELLANEOUSDrug CarriersBinding SitesAdenine[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences021001 nanoscience & nanotechnologyHuman serum albuminGemcitabine3. Good health0104 chemical sciences[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistryLipoproteins LDLMolecular Docking Simulation[ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical scienceschemistryDocking (molecular)Doxorubicin[ CHIM.THEO ] Chemical Sciences/Theoretical and/or physical chemistryBiophysicsMolecular MedicineNanoparticles0210 nano-technologyDrug carrierHydrophobic and Hydrophilic Interactionsmedicine.drugProtein Binding
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Non-Equilibrium Markov State Modeling of the Globule-Stretch Transition

2016

We describe a systematic approach to construct coarse-grained Markov state models from molecular dynamics data of systems driven into a nonequilibrium steady state. We apply this method to study the globule-stretch transition of a single tethered model polymer in shear flow. The folding and unfolding rates of the coarse-grained model agree with the original detailed model. We demonstrate that the folding and unfolding proceeds through the same narrow region of configuration space but along different cycles.

State modelQuantitative Biology::Biomolecules010304 chemical physicsMarkov chainStatistical Mechanics (cond-mat.stat-mech)Non-equilibrium thermodynamicsFOS: Physical sciencesState (functional analysis)Folding (DSP implementation)Condensed Matter - Soft Condensed Matter01 natural sciencesCondensed Matter::Soft Condensed MatterMolecular dynamics0103 physical sciencesSoft Condensed Matter (cond-mat.soft)Configuration spaceStatistical physics010306 general physicsShear flowCondensed Matter - Statistical MechanicsMathematics
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The angle of repose of spherical grains in granular Hele-Shaw cells: A molecular dynamics study

2007

We report the results of three dimensional molecular dynamic simulations on the angle of repose of a sandpile formed by pouring mono-sized cohesionless spherical grains into a granular Hele-Shaw cell. In particular, we are interested to investigate the effects of those variables which may impact significantly on pattern formation of granular mixtures in Hele-Shaw cells. The results indicate that the frictional forces influence remarkably the formation of pile on the grain level. Furthermore, We see that increasing grain insertion rate decreases slightly the angle of repose. We also find that in accordance with experimental results, the cell thickness is another significant factor and the an…

Statistics and ProbabilityCondensed Matter - Materials ScienceMaterials scienceStatistical Mechanics (cond-mat.stat-mech)Pattern formationMaterials Science (cond-mat.mtrl-sci)FOS: Physical sciencesfood and beveragesStatistical and Nonlinear PhysicsFunction (mathematics)MechanicsAngle of reposeMolecular dynamicsGranular matterStatistics Probability and UncertaintyExponential decayCondensed Matter - Statistical Mechanics
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Polydisperse hard spheres: crystallization kinetics in small systems and role of local structure

2016

We study numerically the crystallization of a hard-sphere mixture with 8\% polydispersity. Although often used as a model glass former, for small system sizes we observe crystallization in molecular dynamics simulations. This opens the possibility to study the competition between crystallization and structural relaxation of the melt, which typically is out of reach due to the disparate timescales. We quantify the dependence of relaxation and crystallization times on density and system size. For one density and system size we perform a detailed committor analysis to investigate the suitability of local structures as order parameters to describe the crystallization process. We find that local…

Statistics and ProbabilityMaterials scienceDispersityFOS: Physical sciencesStatistical and Nonlinear Physics02 engineering and technologyHard spheresCondensed Matter - Soft Condensed Matter021001 nanoscience & nanotechnology01 natural sciencesBond orderlaw.inventionReaction coordinateCrystallization kineticsMolecular dynamicsChemical physicslaw0103 physical sciencesSoft Condensed Matter (cond-mat.soft)Relaxation (physics)Statistics Probability and UncertaintyCrystallization010306 general physics0210 nano-technologyJournal of Statistical Mechanics: Theory and Experiment
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Hydrokinetic simulations of nanoscopic precursor films in rough channels

2009

We report on simulations of capillary filling of high-wetting fluids in nano-channels with and without obstacles. We use atomistic (molecular dynamics) and hydrokinetic (lattice-Boltzmann) approaches which point out clear evidence of the formation of thin precursor films, moving ahead of the main capillary front. The dynamics of the precursor films is found to obey a square-root law as the main capillary front, z^2(t) ~ t, although with a larger prefactor, which we find to take the same value for the different geometries (2D-3D) under inspection. The two methods show a quantitative agreement which indicates that the formation and propagation of thin precursors can be handled at a mesoscopic…

Statistics and ProbabilityMesoscopic physicsMaterials scienceParametric analysisCapillary actionFluid Dynamics (physics.flu-dyn)FOS: Physical sciencesStatistical and Nonlinear PhysicsPhysics - Fluid DynamicsMechanicsCapillary fillingSquare (algebra)Settore FIS/02 - Fisica Teorica Modelli e Metodi MatematiciPhysics::Fluid DynamicsMolecular dynamicsPoint (geometry)Statistics Probability and UncertaintyNanoscopic scale
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Structure and dynamics of yukawa systems

1993

Abstract Results of molecular dynamics simulations modelling two component charge stabilized colloidal particles interacting via a Yukawa potential are presented. After cooling, the systems freeze into either substitutionally disordered imperfect crystals or into glasslike states. This freezing is characterized by the divergence of a suitable correlation time due to loss of ergodicity. Describing the structure by bond correlation functions, local orientational ordering is observed in the glassy states which is not present in the liquid. In the liquid the diffusion constant obeys an Arrhenius law. As can be deduced from the van Hove functions, in the crystal the particles only oscillate arou…

Statistics and ProbabilityPhysicsArrhenius equationCondensed matter physicsComponent (thermodynamics)ErgodicityYukawa potentialCharge (physics)Condensed Matter PhysicsFick's laws of diffusionCondensed Matter::Soft Condensed MatterCrystalMolecular dynamicssymbols.namesakesymbolsPhysica A: Statistical Mechanics and its Applications
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Coulomb-interacting billiards in circular cavities

2013

We apply a molecular dynamics scheme to analyze classically chaotic properties of a two-dimensional circular billiard system containing two Coulomb-interacting electrons. As such, the system resembles a prototype model for a semiconductor quantum dot. The interaction strength is varied from the noninteracting limit with zero potential energy up to the strongly interacting regime where the relative kinetic energy approaches zero. At weak interactions the bouncing maps show jumps between quasi-regular orbits. In the strong-interaction limit we find an analytic expression for the bouncing map. Its validity in the general case is assessed by comparison with our numerical data. To obtain a more …

Statistics and ProbabilityPhysicsChaoticGeneral Physics and AstronomyStatistical and Nonlinear PhysicsElectronKinetic energyPotential energyMolecular dynamicsClassical mechanicsModeling and SimulationPhase spaceCoulombDynamical billiardsMathematical PhysicsJournal of Physics A: Mathematical and Theoretical
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Dynamical block analysis in a non-equilibrium system

1991

Abstract We present molecular dynamics simulation results of quenches into the unstable region of a two-dimensional Lennard-Jones system. The evolution of the system from the non-equilibrium state into equilibrium was analyzed with a dynamical block analysis. This can lead to a new approach in the study of non-equilibrium phenomena. We show that with such an analysis one can obtain results on the dynamic evolution as the system evolves, consistent with those obtained from and analysis of the pair-distribution function, structure factor and excess energy. The simulations were carried out on the parallel computer of the condensed matter theory group at the University of Mainz.

Statistics and ProbabilityPhysicsMolecular dynamicsGroup (mathematics)Block (permutation group theory)Statistical physicsFunction (mathematics)State (functional analysis)Condensed Matter PhysicsStructure factorExcess energyPhysica A: Statistical Mechanics and its Applications
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Integral relations, a simplified method to find interfacial resistivities for heat and mass transfer.

2007

International audience; Integral relations were used to predict interface film transfer coefficients for evaporation and condensation. According to these, all coefficients can be calculated for one-component systems, using the thermal resistivity and the enthalpy profile through the interface. The expressions were verified in earlier work using non-equilibrium molecular dynamics simulations for argon-like particles, which interacted with a short-range Lennard-Jones (LJ) spline potential, which becomes zero at about 1.7 times the LJ-diameter. In this paper we verify the validity of these relations for a long-range LJ spline potential which becomes zero at 2.5 times the diameter. In an earlie…

Statistics and ProbabilityPhysicsPhase transitionWork (thermodynamics)CondensationEnthalpyThermodynamics02 engineering and technologyCondensed Matter Physics01 natural sciences[PHYS.PHYS.PHYS-CHEM-PH] Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph][CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistryMolecular dynamicsSpline (mathematics)[CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry[ PHYS.PHYS.PHYS-CHEM-PH ] Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph]Thermal conductivity020401 chemical engineeringMass transfer0103 physical sciences[ CHIM.THEO ] Chemical Sciences/Theoretical and/or physical chemistry[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph]0204 chemical engineering010306 general physicsComputingMilieux_MISCELLANEOUS
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