| 1. |
- Ahadi, Aylin, et al.
(author)
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Modeling and simulation of the mechanical response from nanoindentation test of DNA-filled viral capsids
- 2013
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In: Journal of Biological Physics. - : Springer Science and Business Media LLC. - 0092-0606 .- 1573-0689. ; 39:2, s. 183-199
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Journal article (peer-reviewed)abstract
- Viruses can be described as biological objects composed mainly of two parts: a stiff protein shell called a capsid, and a core inside the capsid containing the nucleic acid and liquid. In many double-stranded DNA bacterial viruses (aka phage), the volume ratio between the liquid and the encapsidated DNA is approximately 1:1. Due to the dominant DNA hydration force, water strongly mediates the interaction between the packaged DNA strands. Therefore, water that hydrates the DNA plays an important role in nanoindentation experiments of DNA-filled viral capsids. Nanoindentation measurements allow us to gain further insight into the nature of the hydration and electrostatic interactions between the DNA strands. With this motivation, a continuum-based numerical model for simulating the nanoindentation response of DNA-filled viral capsids is proposed here. The viral capsid is modeled as large- strain isotropic hyper-elastic material, whereas porous elasticity is adopted to capture the mechanical response of the filled viral capsid. The voids inside the viral capsid are assumed to be filled with liquid, which is modeled as a homogenous incompressible fluid. The motion of a fluid flowing through the porous medium upon capsid indentation is modeled using Darcy's law, describing the flow of fluid through a porous medium. The nanoindentation response is simulated using three-dimensional finite element analysis and the simulations are performed using the finite element code Abaqus. Force-indentation curves for empty, partially and completely DNA-filled capsids are directly compared to the experimental data for bacteriophage lambda. Material parameters such as Young's modulus, shear modulus, and bulk modulus are determined by comparing computed force-indentation curves to the data from the atomic force microscopy (AFM) experiments. Predictions are made for pressure distribution inside the capsid, as well as the fluid volume ratio variation during the indentation test.
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| 2. |
- Cartling, Bo
(author)
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Neuromodulatory control of neocortical microcircuits with activity-dependent short-term synaptic depression
- 2004
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In: Journal of biological physics (Print). - 0092-0606 .- 1573-0689. ; 30:3, s. 261-284
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Journal article (peer-reviewed)abstract
- A biophysical model of a neocortical microcircuit system is formulated and employed in studies of neuromodulatory control of dynamics and function. The model is based on recent observations of reciprocal connections between pyramidal cells and inhibitory interneurons and incorporates a new type of activity-dependent short-term depression of synaptic couplings recently observed. The model neurons are of a low-dimensional type also accounting for neuronal adaptation, i.e. the coupling between neuronal activity and excitability, which can be regulated by various neuromodulators in the brain. The results obtained demonstrate a capacity for neuromodulatory control of dynamical mode linked to functional mode. The functional aspects considered refer to the observed resolution of multiple objects in working memory as well as the binding of different features for the perception of an object. The effects of neuromodulators displayed by the model are in accordance with many observations on neuromodulatory influence on cognitive functions and brain disorders.
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| 3. |
- Cartling, Bo
(author)
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Stochastic and reduced biophysical models of synaptic transmission
- 2000
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In: Journal of biological physics (Print). - 0092-0606 .- 1573-0689. ; 26:2, s. 113-131
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Journal article (peer-reviewed)abstract
- Stochastic and reduced biophysical models of synaptic transmission are formulated and evaluated. The synaptic transmission involves presynaptic facilitation of neurotransmitter release, depletion and recovery of the presynaptic pool of readily releasable vesicles containing neurotransmitter molecules and saturation of postsynaptic receptors of both fast non-NMDA and slow NMDA types. The models are shown to display the principal dynamical characteristics experimentally observed of synaptic transmission. The two main types of neural coding, i.e. rate and temporal coding, can be distinguished by means of different dynamical properties of synaptic transmission determined by initial neurotransmitter release probability and presynaptic firing rate. From the temporal evolution of the postsynaptic membrane potential response to a train of presynaptic action potentials at a sustained firing rate, in particular the steady-state amplitude and steady-state average level of postsynaptic membrane potentials are determined as functions of both initial release probability and presynaptic firing rate. The models are applicable to studies of the primary stages of learning processes and can be extended to incorporate short-term and long-term potentiation in memory consolidation processes.
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| 4. |
- Friedman, Ran, et al.
(author)
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Protein surface dynamics : Interaction with water and small solutes
- 2005
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In: Journal of biological physics (Print). - : Springer Science and Business Media LLC. - 0092-0606 .- 1573-0689. ; 31:3, s. 433-452
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Journal article (peer-reviewed)abstract
- Previous time resolved measurements had indicated that protons could propagate on the surface of a protein, or a membrane, by a special mechanism that enhances the shuttle of the proton towards a specific site [1]. It was proposed that a proper location of residues on the surface contributes to the proton shuttling function. In the present study, this notion was further investigated using molecular dynamics, with only the mobile charge replaced by Na+and Cl− ions. A molecular dynamics simulation of a small globular protein (the S6 of the bacterial ribosome) was carried out in the presence of explicit water molecules and four pairs of Na+ and Cl− ions. A 10 ns simulation indicated that the ions and the protein's surface were in equilibrium, with rapid passage of the ions between the protein's surface and the bulk. Yet it was noted that, close to some domains, the ions extended their duration near the surface, suggesting that the local electrostatic potential prevented them from diffusing to the bulk. During the time frame in which the ions were detained next to the surface, they could rapidly shuttle between various attractor sites located under the electrostatic umbrella. Statistical analysis of molecular dynamics and electrostatic potential/entropy consideration indicated that the detainment state is an energetic compromise between attractive forces and entropy of dilution. The similarity between the motion of free ions next to a protein and the proton transfer on the protein's surface are discussed.
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| 5. |
- Friedman, Ran, et al.
(author)
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Protein Surface - the Dynamics of the Interactions between Protein, Water and Small Solutes
- 2005
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In: Journal of biological physics (Print). - : Springer Science and Business Media LLC. - 0092-0606 .- 1573-0689. ; 31:3-4, s. 433-452
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Journal article (peer-reviewed)abstract
- Previous time resolved measurements had indicated that protons could propagate on the surface of a protein, or a membrane, by a special mechanism that enhances the shuttle of the proton towards a specific site [1]. It was proposed that a proper location of residues on the surface contributes to the proton shuttling function. In the present study, this notion was further investigated using molecular dynamics, with only the mobile charge replaced by Na+ and Cl− ions. A molecular dynamics simulation of a small globular protein (the S6 of the bacterial ribosome) was carried out in the presence of explicit water molecules and four pairs of Na+ and Cl− ions. A 10 ns simulation indicated that the ions and the protein's surface were in equilibrium, with rapid passage of the ions between the protein's surface and the bulk. Yet it was noted that, close to some domains, the ions extended their duration near the surface, suggesting that the local electrostatic potential prevented them from diffusing to the bulk. During the time frame in which the ions were detained next to the surface, they could rapidly shuttle between various attractor sites located under the electrostatic umbrella. Statistical analysis of molecular dynamics and electrostatic potential/entropy consideration indicated that the detainment state is an energetic compromise between attractive forces and entropy of dilution. The similarity between the motion of free ions next to a protein and the proton transfer on the protein's surface are discussed.
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| 6. |
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| 7. |
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| 8. |
- Irbäck, A, et al.
(author)
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Hydrogen bonds, hydrophobicity forces and the character of the collapse transition
- 2001
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In: Journal of Biological Physics. - 0092-0606. ; 27:2-3, s. 79-169
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Journal article (peer-reviewed)abstract
- We study the thermodynamic behavior of a model protein with 54 amino acidsthat is designed to form a three-helix bundle in its native state. The model contains three types of amino acids and five to six atoms per amino acid, and has the Ramachandran torsion angles as its only degrees of freedom.The force field is based on hydrogen bonds and effective hydrophobicity forces. We study how the character of the collapse transition depends on the strengths of these forces. For a suitable choice of these two parameters, it is found that the collapse transition is first-order-like and coincides with the folding transition. Also shown is that the corresponding one- and two-helix segments make less stable secondary structure than the three-helix sequence.
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| 9. |
- Manz, Christoph, et al.
(author)
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Exploring the energy landscape of a SAM-I riboswitch
- 2021
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In: Journal of biological physics (Print). - : Springer. - 0092-0606 .- 1573-0689. ; 47:4, s. 371-386
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Journal article (peer-reviewed)abstract
- SAM-I riboswitches regulate gene expression through transcription termination upon binding a S-adenosyl-L-methionine (SAM) ligand. In previous work, we characterized the conformational energy landscape of the full-length Bacillus subtilis yitJ SAM-I riboswitch as a function of Mg2+ and SAM ligand concentrations. Here, we have extended this work with measurements on a structurally similar ligand, S-adenosyl-l-homocysteine (SAH), which has, however, a much lower binding affinity. Using single-molecule Forster resonance energy transfer (smFRET) microscopy and hidden Markov modeling (HMM) analysis, we identified major conformations and determined their fractional populations and dynamics. At high Mg2+ concentration, FRET analysis yielded four distinct conformations, which we assigned to two terminator and two antiterminator states. In the same solvent, but with SAM added at saturating concentrations, four states persisted, although their populations, lifetimes and interconversion dynamics changed. In the presence of SAH instead of SAM, HMM revealed again four well-populated states and, in addition, a weakly populated 'hub' state that appears to mediate conformational transitions between three of the other states. Our data show pronounced and specific effects of the SAM and SAH ligands on the RNA conformational energy landscape. Interestingly, both SAM and SAH shifted the fractional populations toward terminator folds, but only gradually, so the effect cannot explain the switching action. Instead, we propose that the noticeably accelerated dynamics of interconversion between terminator and antiterminator states upon SAM binding may be essential for control of transcription.
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| 10. |
- Nevsten, Pernilla, et al.
(author)
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Chemical mapping of DNA and counter-ion content inside phage by energy-filtered TEM
- 2012
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In: Journal of Biological Physics. - : Springer Science and Business Media LLC. - 0092-0606 .- 1573-0689. ; 38:2, s. 229-240
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Journal article (peer-reviewed)abstract
- Double-stranded DNA in many bacterial viruses (phage) is strongly confined, which results in internal genome pressures of tens of atmospheres. This pressure is strongly dependent on local ion concentration and distribution within the viral capsid. Here, we have used electron energy loss spectroscopy (EELS), energy-filtered TEM (EFTEM) and X-ray energy dispersive spectroscopy to provide such chemical information from the capsid and the phage tail through which DNA is injected into the cell. To achieve this, we have developed a method to prepare thin monolayers of self-supporting virus/buffer films, suitable for EELS and EFTEM analysis. The method is based on entrapment of virus particles at air-liquid interfaces; thus, the commonly used method of staining by heavy metal salts can be avoided, eliminating the risk for chemical artifacts. We found that Mg2 + concentration was approximately 2-4 times higher in the DNA-filled capsid than in the surrounding TM buffer (containing 10 mM Mg2 + ). Furthermore, we also analyzed the DNA content inside the phage tail by mapping phosphorus and magnesium.
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