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- Lyubartsev, Alexander P., et al.
(författare)
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Systematic hierarchical coarse-graining with the inverse Monte Carlo method
- 2015
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 143:24
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Tidskriftsartikel (refereegranskat)abstract
- We outline our coarse-graining strategy for linking micro-and mesoscales of soft matter and biological systems. The method is based on effective pairwise interaction potentials obtained in detailed ab initio or classical atomistic Molecular Dynamics (MD) simulations, which can be used in simulations at less accurate level after scaling up the size. The effective potentials are obtained by applying the inverse Monte Carlo (IMC) method [A. P. Lyubartsev and A. Laaksonen, Phys. Rev. E 52(4), 3730-3737 (1995)] on a chosen subset of degrees of freedom described in terms of radial distribution functions. An in-house software package MagiC is developed to obtain the effective potentials for arbitrary molecular systems. In this work we compute effective potentials to model DNA-protein interactions (bacterial LiaR regulator bound to a 26 base pairs DNA fragment) at physiological salt concentration at a coarse-grained (CG) level. Normally the IMC CG pair-potentials are used directly as look-up tables but here we have fitted them to five Gaussians and a repulsive wall. Results show stable association between DNA and the model protein as well as similar position fluctuation profile.
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- Fossépré, Mathieu, et al.
(författare)
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Multiscale design of coarse-grained elastic network-based potentials for the mu opioid receptor
- 2016
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Ingår i: Journal of Molecular Modeling. - : Springer Science and Business Media LLC. - 1610-2940 .- 0948-5023. ; 22:9
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Tidskriftsartikel (refereegranskat)abstract
- Despite progress in computer modeling, most biological processes are still out of reach when using all-atom (AA) models. Coarse-grained (CG) models allow classical molecular dynamics (MD) simulations to be accelerated. Although simplification of spatial resolution at different levels is often investigated, simplification of the CG potential in itself has been less common. CG potentials are often similar to AA potentials. In this work, we consider the design and reliability of purely mechanical CG models of the mu opioid receptor (mu OR), a G protein-coupled receptor (GPCR). In this sense, CG force fields (FF) consist of a set of holonomic constraints guided by an elastic network model (ENM). Even though ENMs are used widely to perform normal mode analysis (NMA), they are not often implemented as a single FF in the context of MD simulations. In this work, various ENM-like potentials were investigated by varying their force constant schemes and connectivity patterns. A method was established to systematically parameterize ENM-like potentials at different spatial resolutions by using AA data. To do so, new descriptors were introduced. The choice of conformation descriptors that also include flexibility information is important for a reliable parameterization of ENMs with different degrees of sensitivity. Hence, ENM-like potentials, with specific parameters, can be sufficient to accurately reproduce AA MD simulations of mu OR at highly coarse-grained resolutions. Therefore, the essence of the flexibility properties of mu OR can be captured with simple models at different CG spatial resolutions, opening the way to mechanical approaches to understanding GPCR functions.
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- Fossépré, Mathieu, et al.
(författare)
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On the Modularity of the Intrinsic Flexibility of the mu Opioid Receptor : A Computational Study
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115856-
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Tidskriftsartikel (refereegranskat)abstract
- The mu opioid receptor (mu OR), the principal target to control pain, belongs to the G protein-coupled receptors (GPCRs) family, one of the most highlighted protein families due to their importance as therapeutic targets. The conformational flexibility of GPCRs is one of their essential characteristics as they take part in ligand recognition and subsequent activation or inactivation mechanisms. It is assessed that the intrinsic mechanical properties of the mu OR, more specifically its particular flexibility behavior, would facilitate the accomplishment of specific biological functions, at least in their first steps, even in the absence of a ligand or any chemical species usually present in its biological environment. The study of the mechanical properties of the mu OR would thus bring some indications regarding the highly efficient ability of the mu OR to transduce cellular message. We therefore investigate the intrinsic flexibility of the mu OR in its apo-form using all-atom Molecular Dynamics simulations at the sub-microsecond time scale. We particularly consider the mu OR embedded in a simplified membrane model without specific ions, particular lipids, such as cholesterol moieties, or any other chemical species that could affect the flexibility of the mu OR. Our analyses highlighted an important local effect due to the various bendability of the helices resulting in a diversity of shape and volume sizes adopted by the mu OR binding site. Such property explains why the mu OR can interact with ligands presenting highly diverse structural geometry. By investigating the topology of the mu OR binding site, a conformational global effect is depicted: the correlation between the motional modes of the extra-and intracellular parts of mu OR on one hand, along with a clear rigidity of the central mu OR domain on the other hand. Our results show how the modularity of the mu OR flexibility is related to its preability to activate and to present a basal activity.
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- Larin, Alexander V., et al.
(författare)
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Oxide clusters as source of the third oxygen atom for the formation of carbonates in alkaline earth dehydrated zeolites
- 2011
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Ingår i: Journal of Catalysis. - : Elsevier BV. - 0021-9517 .- 1090-2694. ; 281:2, s. 212-221
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Tidskriftsartikel (refereegranskat)abstract
- In our paper, we show that carbonates can be formed with almost no energetic barrier from CO(2) and metal-oxide binuclear MO(x)M species (M = Mg, Ca, Sr, Ba, with X = 1-4, depending on the cation) in alkaline earth zeolites, mordenite (MOR) and phillipsite (PHI), on the basis of quantum mechanical density functional theory (DFT) calculations at both isolated cluster and 3D periodic levels. The participation of MO(x)M species (X = 1 and 3) explains the source of the third O atom in CO(3) species in dehydrated zeolites, on the basis of a good agreement between the calculated and experimental positions of the asymmetric and symmetric CO(3) vibration bands, of the ratio of their intensities, and of the weak dependence versus the cation and framework type. The reaction of formation of dimethylcarbonate from CaCO(3)Ca in the 8-membered (8R) ring of MOR and methanol has also been considered, suggesting the carbonate activity as the source of CO(2) at elevated temperatures.
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- Naome, Aymeric, et al.
(författare)
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A Coarse-Grained Simulation Study of the Structures, Energetics, and Dynamics of Linear and Circular DNA with Its Ions
- 2015
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 11:6, s. 2813-2826
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the structural, energetics, and dynamical properties of a variety of linear and circular DNA fragments using a solvent-mediated coarse-grained (CG) model of DNA with explicit ions recently developed by us [Naome et al., J. Chem. Theory Comput., 2014, 10, 3541-3549]. We particularly examined the treatment of electrostatics and determined that a large cutoff is necessary to properly reproduce the DNA flexibility. Moreover, it is crucial to include long-ranged electrostatic interactions: a Particle Mesh Ewald scheme at low resolution is sufficient to avoid structural artifacts. We calculated the ring closure probabilities, as a j-factors, for DNA fragments of different lengths from equilibrium, as well. as restrained molecular dynamics (MD) simulations. The latter force integration method provided accurate results without model fitting. We generated topology and energy maps for DNA minicircles of various lengths and helical densities, at low and high ion concentrations. A general trend for structure compaction is observed, driven by an increase in writhing as the ionic concentration increases. Finally, we applied a reconstruction procedure to generate detailed molecular structures from the various superhelical conformations generated by the CG MD of the DNA minicircles. These pre-equilibrated reconstructed atomistic structures can serve as starting material for atomistic simulations.
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- Naomé, Aymeric, et al.
(författare)
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A Solvent-Mediated Coarse-Grained Model of DNA Derived with the Systematic Newton Inversion Method
- 2014
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 10:8, s. 3541-3549
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Tidskriftsartikel (refereegranskat)abstract
- We present a new class of coarse-grained (CG) force fields (FFs) for B-DNA with explicit ions suited for large-scale mesoscale simulations at microsecond micrometer scale using a wide spectrum of particle simulation methods from molecular dynamics to dissipative particle dynamics. The effective solvent-mediated pairwise interactions making up the FFs are obtained by inverting radial distribution functions and other particle particle distributions obtained from all-atom simulations of numbers of octadecamer DNA fragments from the Ascona B-DNA library. The inverse Monte Carlo (IMC) method, later known as Newton inversion (NI) (Lyubartsev, A. P.; Laaksonen, A. Phys. Rev. E, 1995, 52, 3730-3737), was used together with the iterative Boltzmann inversion (IBI) scheme to compute the effective CG potentials. We show that this systematic structure-based approach is capable of providing converged potentials that accurately reproduce the structural features of the underlying atomistic system within a few percents of relative difference. We also show that a simple one-site-per-nucleotide model with 10 intramolecular pair interaction potentials is able to reproduce key features of DNA, for example, the persistence length and its dependence on the ionic concentration, experimentally determined around 50 nm at physiological salt concentration.
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- Naomé, Aymeric, et al.
(författare)
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Molecular Dynamics Simulation of 8-Oxoguanine Containing DNA Fragments Reveals Altered Hydration and Ion Binding Patterns
- 2010
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:14, s. 4789-4801
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Tidskriftsartikel (refereegranskat)abstract
- We present results of molecular dynamics (MD) simulations of a double-stranded DNA fragment of sequence 5'-d(CGCGAGTTCGCG)-3' and 3'-d(GCGCTCAAGCGC)-5' in its native form and altered with guanine in the G6/C19 base pair replaced by 8-oxoguanine (8oxoG). DNA was simulated in solution with Na+ counterions and explicit water molecules. Trajectories were analyzed for radial distribution functions (RDFs), spatial distribution functions (SDFs), residence times, and occupancies, for both water and ions. Structural parameters of DNA fragments were also considered. Particularly, we report sensible differences in the statistical and dynamical behavior of water and ions between the healthy and lesion containing models. Structural features such as sugar phosphate backbone torsion angles also significantly differ. We conclude that 8oxoG noticeably modifies its close environment and that the observed changes in the vicinity of the lesion site might help the enzymes in charge of cleansing 8oxoG from human DNA to locate the aberration in its intrahelical context. This work supports the existence of a determinant early recognition mode of 8oxoG; for hOGG1.
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