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animation:workshops:2011:coarsegrain [2013/01/15 16:16] sbarends [Coarse-Grain Mechanics of DNA: Part II From Electrons to Oligomers] |
animation:workshops:2011:coarsegrain [2015/01/07 10:04] (Version actuelle) |
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| ====== Coarse-Grain Mechanics of DNA: Part II From Electrons to Oligomers ====== | ====== Coarse-Grain Mechanics of DNA: Part II From Electrons to Oligomers ====== | ||
| - | Location: CECAM-HQ-EPFL, Lausanne, Switzerland \\ | + | Location: CECAM-HQ-EPFL, Lausanne, Switzerland \\ |
| - | August 30, 2011 to September 2, 2011 | + | August 30, 2011 to September 2, 2011 \\ |
| + | [[http://www.cecam.org/workshop-0-539.html|Website of the event]] | ||
| Organisers: | Organisers: | ||
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| ===== State of the art ===== | ===== State of the art ===== | ||
| - | ==== Atomistic Molecular Dynamics Simulations of Short Oligomers ==== | + | |
| + | === Atomistic Molecular Dynamics Simulations of Short Oligomers === | ||
| The year 2011 will be the tenth anniversary of the forming of the ABC (or Ascona B-DNA Consortium) collaboration. The ABC was born at an interdisciplinary workshop organized by John Maddocks. The idea was that by pooling computational resources between groups, a database of entirely consistent simulations of DNA oligomers covering "all possible" sequence-dependence could be constructed. The most recent ABC publication [2], which is based on a data set of nearly 5microseconds of simulation time of 39 different 18 base-pair oligomers, is only now starting to approach that goal, and of course much was learnt along the way. For example, previous ABC data sets revealed serious limitations of the underlying Amber atomistic force field, which lead to a re-parametrization from quantum simulations [3]. The current data set has no known inconsistencies with experimental data, and has various specific predictions, for example bimodal distribution of twist at certain specific base-pair steps. | The year 2011 will be the tenth anniversary of the forming of the ABC (or Ascona B-DNA Consortium) collaboration. The ABC was born at an interdisciplinary workshop organized by John Maddocks. The idea was that by pooling computational resources between groups, a database of entirely consistent simulations of DNA oligomers covering "all possible" sequence-dependence could be constructed. The most recent ABC publication [2], which is based on a data set of nearly 5microseconds of simulation time of 39 different 18 base-pair oligomers, is only now starting to approach that goal, and of course much was learnt along the way. For example, previous ABC data sets revealed serious limitations of the underlying Amber atomistic force field, which lead to a re-parametrization from quantum simulations [3]. The current data set has no known inconsistencies with experimental data, and has various specific predictions, for example bimodal distribution of twist at certain specific base-pair steps. | ||
| - | ==== Atomistic Molecular Dynamics Simulations of DNA Minicircles and Experiment: ==== | + | === Atomistic Molecular Dynamics Simulations of DNA Minicircles and Experiment: === |
| The study of J-factors, or the probability of formation of DNA minicircles, is a classic technique for studying DNA mechanics. And minicircle formation has even been proposed as a way to determine experimentally the sequence-dependent mechanical properties of DNA [4]. In particular some specific sequences were observed to cyclize remarkably efficiently compared to predictions made by standard, sequence-independent theories [5], although there is still some controversy over the experimental results [6,7]. Motivated by these results there have been two published molecular dynamics simulations of full minicircles [8,9], the first of which observed localized kink deformations of the DNA duplex, remarkably similar to those discussed theoretically thirty years previously [10]. The 3D conformations of slightly longer DNA minicircles can be observed using stereo-cryo-EM [11, 12] although the method is very close to the limits of resolution. Nevertheless after the introduction of new statistical tests for curves in 3D, a statistically significant difference in the fluctuations of two minicircles formed from two different sequences could be observed [13]. | The study of J-factors, or the probability of formation of DNA minicircles, is a classic technique for studying DNA mechanics. And minicircle formation has even been proposed as a way to determine experimentally the sequence-dependent mechanical properties of DNA [4]. In particular some specific sequences were observed to cyclize remarkably efficiently compared to predictions made by standard, sequence-independent theories [5], although there is still some controversy over the experimental results [6,7]. Motivated by these results there have been two published molecular dynamics simulations of full minicircles [8,9], the first of which observed localized kink deformations of the DNA duplex, remarkably similar to those discussed theoretically thirty years previously [10]. The 3D conformations of slightly longer DNA minicircles can be observed using stereo-cryo-EM [11, 12] although the method is very close to the limits of resolution. Nevertheless after the introduction of new statistical tests for curves in 3D, a statistically significant difference in the fluctuations of two minicircles formed from two different sequences could be observed [13]. | ||
| - | ==== Rigid base and base-pair models: ==== | + | === Rigid base and base-pair models: === |
| A standard model of the elasticity of double-helical DNA on the few nm length scale is the rigid base-pair model (rbpm), whose conformation variables are the relative positions and orientations of adjacent base pairs [14]. Corresponding sequence-dependent local elastic potentials have been obtained from (combinations of) all-atom MD simulation and from high-resolution crystal structure data [15,16,17,18] and have been used with some success to model DNA-protein binding [17] and nucleosome positioning [18, 19]. Nevertheless the analysis of [20] has shown that at length scales of a few tens of base-pairs, a rbpm with a localized energy is not consistent with molecular dynamics data sets of the type obtained in [2], while a rigid base model with localized interactions is consistent with molecular dynamics data. | A standard model of the elasticity of double-helical DNA on the few nm length scale is the rigid base-pair model (rbpm), whose conformation variables are the relative positions and orientations of adjacent base pairs [14]. Corresponding sequence-dependent local elastic potentials have been obtained from (combinations of) all-atom MD simulation and from high-resolution crystal structure data [15,16,17,18] and have been used with some success to model DNA-protein binding [17] and nucleosome positioning [18, 19]. Nevertheless the analysis of [20] has shown that at length scales of a few tens of base-pairs, a rbpm with a localized energy is not consistent with molecular dynamics data sets of the type obtained in [2], while a rigid base model with localized interactions is consistent with molecular dynamics data. | ||
| - | ==== Sequence-dependent continuum mechanics models: ==== | + | === Sequence-dependent continuum mechanics models: === |
| Beyond the 100nm scale, DNA is successfully described by a worm like chain model with homogeneous elastic properties [21], which can be determined via a systematic coarse-graining procedure from the rbpm [22]. Modifications to model kinking have also been proposed [23]. On the wormlike chain level a systematic treatment of small fluctuations (semi classical approximation) of the statistical mechanics of chains is now available [24,25].Sequence-dependent continuum models ignoring fluctuations have been applied to model cyclization data [26]. | Beyond the 100nm scale, DNA is successfully described by a worm like chain model with homogeneous elastic properties [21], which can be determined via a systematic coarse-graining procedure from the rbpm [22]. Modifications to model kinking have also been proposed [23]. On the wormlike chain level a systematic treatment of small fluctuations (semi classical approximation) of the statistical mechanics of chains is now available [24,25].Sequence-dependent continuum models ignoring fluctuations have been applied to model cyclization data [26]. | ||