Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Abstract: The chemical and biological sciences face unprecedented opportunities in the 21st century. A confluence of factors from parallel universes - advances in experimental techniques in biomolecular structure determination, progress in theoretical modeling and simulation for large biological systems, and breakthroughs in computer technology - has opened new avenues of opportunity as never before. Now, experimental data can be interpreted and further analysed by modeling, and predictions from any approach can be tested and advanced through companion methodologies and technologies. This two volume set describes innovations in biomolecular modeling and simulation, in both the algorithmic and application fronts. With contributions from experts in the field, the books describe progress and innovation in areas including: simulation algorithms for dynamics and enhanced configurational sampling, force field development, implicit solvation models, coarse-grained models, quantum-mechanical simulations, protein folding, DNA polymerase mechanisms, nucleic acid complexes and simulations, RNA structure analysis and design and other important topics in structural biology modeling. The books are aimed at graduate students and experts in structural biology and chemistry and the emphasis is on reporting innovative new approaches rather than providing comprehensive reviews on each subject.
    Type of Publication: Book chapter
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: ENERGIES ; EXPRESSION ; Germany ; GENE ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; DNA ; IMPACT ; SIMULATION ; BINDING ; CHROMATIN ; gene expression ; ENERGY ; EXCHANGE ; ANGSTROM RESOLUTION ; MONTE-CARLO ; ORDER ; CHAIN ; higher-order structure ; LINKER HISTONE ; nucleosomes ; PROTOCOL ; interaction ; NUCLEOSOME ; MONTE-CARLO-SIMULATION ; USA ; CHROMATIN FIBER ; COMPUTER-SIMULATION ; SCANNING FORCE MICROSCOPY ; computer simulations ; CORE PARTICLE ; SHAPE ; COOPERATIVE BINDING ; NUCLEOSOME REPEAT LENGTH
    Abstract: The folding of the nucleosome chain into a chromatin fiber modulates DNA accessibility and is therefore an important factor for the control of gene expression. The fiber conformation depends crucially on the interaction between individual nucleosomes. However, this parameter has not been accurately determined experimentally, and it is affected by posttranslational histone modi. cations and binding of chromosomal proteins. Here, the effect of different internucleosomal interaction strengths on the fiber conformation was investigated by Monte Carlo computer simulations. The fiber geometry was modeled to fit that of chicken erythrocyte chromatin, which has been examined in numerous experimental studies. In the Monte Carlo simulation, the nucleosome shape was described as an oblate spherocylinder, and a replica exchange protocol was developed to reach thermal equilibrium for a broad range of internucleosomal interaction energies. The simulations revealed the large impact of the nucleosome geometry and the nucleosome repeat length on the compaction of the chromatin fiber. At high internucleosomal interaction energies, a lateral self-association of distant fiber parts and an interdigitation of nucleosomes were apparent. These results identify key factors for the control of the compaction and higher order folding of the chromatin fiber
    Type of Publication: Journal article published
    PubMed ID: 18658212
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Abstract: The three-dimensional structure of chromatin affects DNA accessibility and is therefore a key regulator of gene expression. However, the path of the DNA between consecutive nucleosomes, and the resulting chromatin fiber organization remain controversial. The conformational space available for the folding of the nucleosome chain has been analytically described by phase diagrams with a two-angle model, which describes the chain trajectory by a DNA entry-exit angle at the nucleosome and a torsion angle between consecutive nucleosomes. Here, a novel type of numerical phase diagrams is introduced that relates the geometric phase space to the energy associated with a given chromatin conformation. The resulting phase diagrams revealed differences in the energy landscape that reflect the probability of a given conformation to form in thermal equilibrium. Furthermore, we investigated the effects of entropy and additional degrees of freedom in the dynamic phase diagrams by performing Monte Carlo simulations of the initial chain trajectories. Using our approach, we were able to demonstrate that conformations that initially were geometrically impossible could evolve into energetically favorable states in thermal equilibrium due to DNA bending and torsion. In addition, dynamic phase diagrams were applied to identify chromatin fibers that reflect certain experimentally determined features.
    Type of Publication: Journal article published
    PubMed ID: 20303860
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: SIMULATIONS ; SIMULATION ; SPECTROSCOPY ; CHROMATIN ; FIBER ; ENERGETICS ; MONTE-CARLO ; CHROMATIN FIBER
    Type of Publication: Journal article published
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: SIMULATIONS ; MODEL ; transcription ; DYNAMICS ; CHROMATIN ; REVEALS ; CHROMATIN STRUCTURE ; PROTEIN INTERACTIONS ; higher-order structure ; LINKER HISTONE ; NUCLEOSOME ; Monte Carlo simulation ; COMPUTER-SIMULATION ; DNA TARGET SITES ; force spectroscopy ; NUCLEOSOME REPEAT LENGTH ; H4-K16 ACETYLATION
    Abstract: The folding of the nucleosome chain into a chromatin fiber is a central factor for controlling the DNA access of protein factors involved in transcription, DNA replication and repair. Force spectroscopy experiments with chromatin fibers are ideally suited to dissect the interactions that drive this process, and to probe the underlying fiber conformation. However, the interpretation of the experimental data is fraught with difficulties due to the complex interplay of the nucleosome geometry and the different energy terms involved. Here, we apply a Monte Carlo simulation approach to derive virtual chromatin fiber force spectroscopy curves. In the simulations, the effect of the nucleosome geometry, repeat length, nucleosome-nucleosome interaction potential, and the unwrapping of the DNA from the histone protein core on the shape of the force-extension curves was investigated. These simulations provide a framework for the evaluation of experimental data sets. We demonstrate how the relative contributions of DNA bending and twisting, nucleosome unstacking and unwrapping the nucleosomal DNA from the histone octamer can be dissected for a given fiber geometry
    Type of Publication: Journal article published
    PubMed ID: 21294108
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: Germany ; MODEL ; DENSITY ; GENOME ; RESOLUTION ; DNA ; SIMULATION ; BINDING ; CHROMATIN ; CRYSTAL-STRUCTURE ; MONTE-CARLO ; MOLECULAR-DYNAMICS ; TERMINAL DOMAIN ; CHAIN ; RE ; DEPENDENCE ; higher-order structure ; LINKER HISTONE ; nucleosomes ; interaction ; NUCLEOSOME ; MONTE-CARLO-SIMULATION ; MASS ; USA ; CHROMATIN FIBER ; COMPUTER-SIMULATION ; SCANNING FORCE MICROSCOPY ; LINKER HISTONE H1 ; AGREEMENT ; SHAPE ; interactions ; COOPERATIVE BINDING ; GLOBULAR DOMAIN
    Abstract: Based on model structures with atomic resolution, a coarse-grained model for the nucleosome geometry was implemented. The dependence of the chromatin fiber conformation on the spatial orientation of nucleosomes and the path and length of the linker DNA was systematically explored by Monte Carlo simulations. Two fiber types were analyzed in detail that represent nucleosome chains without and with linker histones, respectively: two-start helices with crossed-linker DNA (CL conformation) and interdigitated one-start helices (ID conformation) with different nucleosome tilt angles. The CL conformation was derived from a tetranucleosome crystal structure that was extended into a fiber. At thermal equilibrium, the fiber shape persisted but relaxed into a structure with a somewhat lower linear mass density of 3.1 +/- 0.1 nucleosomes/11 nm fiber. Stable ID fibers required local nucleosome tilt angles between 40 degrees and 60 degrees. For these configurations, much higher mass densities of up to 7.9 +/- 0.2 nucleosomes/11 nm fiber were obtained. A model is proposed, in which the transition between a CL and ID fiber is mediated by relatively small changes of the local nucleosome geometry. These were found to be in very good agreement with changes induced by linker histone H1 binding as predicted from the high resolution model structures
    Type of Publication: Journal article published
    PubMed ID: 18212006
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: mechanisms ; REVEALS ; FLEXIBILITY ; ANGSTROM RESOLUTION ; RESONANCE ENERGY-TRANSFER ; CHROMATIN FIBER ; INDIVIDUAL NUCLEOSOMES ; CORE PARTICLE ; ACCESSIBILITY ; TAIL DOMAINS ; FORCE
    Abstract: The nucleosome complex of DNA wrapped around a histone protein octamer organizes the genome of eukaryotes and regulates the access of protein factors to the DNA. We performed molecular dynamics simulations of the nucleosome in explicit water to study the dynamics of its histone-DNA interactions. A high-resolution histone-DNA interaction map was derived that revealed a five-nucleotide periodicity, in which the two DNA strands of the double helix made alternating contacts. On the 100-ns timescale, the histone tails mostly maintained their initial positions relative to the DNA, and the spontaneous unwrapping of DNA was limited to 1-2 basepairs. In steered molecular dynamics simulations, external forces were applied to the linker DNA to investigate the unwrapping pathway of the nucleosomal DNA. In comparison with a nucleosome without the unstructured N-terminal histone tails, the following findings were obtained: 1), Two main barriers during unwrapping were identified at DNA position +/- 70 and +/- 45 basepairs relative to the central DNA basepair at the dyad axis. 2), DNA interactions of the histone H3 N-terminus and the histone H2A C-terminus opposed the initiation of unwrapping. 3), The N-terminal tails of H2A, H2B, and H4 counteracted the unwrapping process at later stages and were essential determinants of nucleosome dynamics. Our detailed analysis of DNA-histone interactions revealed molecular mechanisms for modulating access to nucleosomal DNA via conformational rearrangements of its structure
    Type of Publication: Journal article published
    PubMed ID: 22004754
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...