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Philippe H Hunenberger - One of the best experts on this subject based on the ideXlab platform.

  • Vase‐Kite Equilibrium of Resorcin[4]arene Cavitands Investigated Using Molecular Dynamics Simulations with Ball‐and‐Stick Local Elevation Umbrella Sampling
    Helvetica Chimica Acta, 2019
    Co-Authors: David Hahn, Jovana V. Milić, Philippe H Hunenberger
    Abstract:

    A key feature of resorcin[4]arene cavitands is their ability to switch between a closed/contracted (Vase) and an open/expanded (Kite) conformation. The mechanism and dynamics of this interconversion remains, however, elusive. In the present study, the Vase-Kite transitions of a quinoxaline-based and of a dinitrobenzene-based resorcin[4]arene are investigated using molecular dynamics (MD) simulations in three environments (vacuum, chloroform, and toluene) and at three temperatures (198.15, 248.15, and 298.15K). The challenge of sampling the Vase-Kite transition, which occurs experimentally on the millisecond time scale, is overcome by calculating relative free energies using ball-and stick Local Elevation umbrella sampling (B&S-LEUS) to enhance the statistics on the relevant states and to promote interconversion transitions. Associated unbiased MD simulations also evidence for the first time a complete Vase-to-Kite transition, as well as transitions between degenerate Kite1 and Kite2 forms and solvent-exchange events. The calculated Vase-to-Kite free-energy changes G are in qualitative agreement with the experimental magnitudes and trends. The level of quantitative agreement is, however, limited by the force-field accuracy and, in particular, by the approximate treatment of intramolecular interactions at the classical level. The results are in line with a less stable Vase state for the dinitrobenzene compared to the quinoxaline compound, and a negative entropy change S for the Vase-to-Kite transition of the latter compound. Relative free energies calculated for intermediates also suggest that the Vase-Kite transition does not follow a concerted mechanism, but an asynchronous one with sequential opening of the flaps. In particular, the conformation involving two adjacent flaps open in a parallel direction (cis-p) represents a likely intermediate, which has not been observed experimentally to date

  • Multistate λ-Local-Elevation umbrella-sampling (MS-λ-LEUS): method and application to the complexation of cations by crown ethers.
    Journal of chemical theory and computation, 2015
    Co-Authors: Noah S. Bieler, Jan P Tschopp, Philippe H Hunenberger
    Abstract:

    An extension of the λ-Local-Elevation umbrella-sampling (λ-LEUS) scheme [ Bieler et al. J. Chem. Theory Comput. 2014 , 10 , 3006 ] is proposed to handle the multistate (MS) situation, i.e. the calculation of the relative free energies of multiple physical states based on a single simulation. The key element of the MS-λ-LEUS approach is to use a single coupling variable Λ controlling successive pairwise mutations between the states of interest in a cyclic fashion. The Λ variable is propagated dynamically as an extended-system variable, using a coordinate transformation with plateaus and a memory-based biasing potential as in λ-LEUS. Compared to other available MS schemes (one-step perturbation, enveloping distribution sampling and conventional λ-dynamics) the proposed method presents a number of important advantages, namely: (i) the physical states are visited explicitly and over finite time periods; (ii) the extent of unphysical space required to ensure transitions is kept minimal and, in particular, one-dimensional; (iii) the setup protocol solely requires the topologies of the physical states; and (iv) the method only requires limited modifications in a simulation code capable of handling two-state mutations. As an initial application, the absolute binding free energies of five alkali cations to three crown ethers in three different solvents are calculated. The results are found to reproduce qualitatively the main experimental trends and, in particular, the experimental selectivity of 18C6 for K(+) in water and methanol, which is interpreted in terms of opposing trends along the cation series between the solvation free energy of the cation and the direct electrostatic interactions within the complex.

  • Communication: estimating the initial biasing potential for λ-Local-Elevation umbrella-sampling (λ-LEUS) simulations via slow growth.
    The Journal of chemical physics, 2014
    Co-Authors: Noah S. Bieler, Philippe H Hunenberger
    Abstract:

    In a recent article [Bieler et al. , J. Chem. Theory Comput.10, 3006–3022 (2014)], we introduced a combination of the λ-dynamics (λD) approach for calculating alchemical free-energy differences and of the Local-Elevation umbrella-sampling (LEUS) memory-based biasing method to enhance the sampling along the alchemical coordinate. The combined scheme, referred to as λ-LEUS, was applied to the perturbation of hydroquinone to benzene in water as a test system, and found to represent an improvement over thermodynamic integration (TI) in terms of sampling efficiency at equivalent accuracy. However, the preoptimization of the biasing potential required in the λ-LEUS method requires “filling up” all the basins in the potential of mean force. This introduces a non-productive pre-sampling time that is system-dependent, and generally exceeds the corresponding equilibration time in a TI calculation. In this letter, a remedy is proposed to this problem, termed the slow growth memory guessing (SGMG) approach. Instead of initializing the biasing potential to zero at the start of the preoptimization, an approximate potential of mean force is estimated from a short slow growth calculation, and its negative used to construct the initial memory. Considering the same test system as in the preceding article, it is shown that of the application of SGMG in λ-LEUS permits to reduce the preoptimization time by about a factor of four.

  • Local Elevation Umbrella Sampling Applied to the Calculation of Alchemical Free-Energy Changes via λ-Dynamics: The λ-LEUS Scheme.
    Journal of chemical theory and computation, 2014
    Co-Authors: Noah S. Bieler, Rico Häuselmann, Philippe H Hunenberger
    Abstract:

    When using molecular dynamics (MD) simulations for the calculation of alchemical free-energy changes, the extended-dynamics method called λ-dynamics (λD) in its currently available implementations does not compare very favorably with thermodynamic integration (TI) in terms of robustness, efficiency, and accuracy, although it is in principle easier to set up, postprocess, and automatize. In the present article, the main shortcomings of the λD approach are carefully analyzed, and possible remedies are proposed. The resulting scheme, called λ-LEUS, involves: (i) the use of a simple noninvertible coordinate transformation ensuring a finite sampling of the two physical end states; (ii) the application of the Local Elevation umbrella sampling (LEUS) memory-based biasing scheme to enforce homogeneous sampling and overcome barriers along the alchemical coordinate; (iii) recommendations concerning the choice of the mass parameter and of the temperature-coupling scheme for this coordinate; (iv) the use of a second-order splines basis set for the memory-based biasing functions. The λ-LEUS scheme is described and tested considering the perturbation of hydroquinone to benzene in water. The results are compared to those of TI calculations and exhibit a superior accuracy-to-efficiency ratio, presumably because dynamic variations in the alchemical coordinate open up pathways to circumvent orthogonal barriers, these pathways being inaccessible when the coordinate is constrained. Therefore, λ-LEUS combines the practical advantages of λD with the robustness of TI, simultaneously affording a slightly enhanced computational efficiency.

  • Ball-and-Stick Local Elevation Umbrella Sampling: Molecular Simulations Involving Enhanced Sampling within Conformational or Alchemical Subspaces of Low Internal Dimensionalities, Minimal Irrelevant Volumes, and Problem-Adapted Geometries
    Journal of chemical theory and computation, 2010
    Co-Authors: Halvor S Hansen, Philippe H Hunenberger
    Abstract:

    A new method, ball-and-stick Local Elevation umbrella sampling (BS (B) representation of the relevant states by means of spheres ("balls"), each associated with a biasing potential involving a one-dimensional radial memory-based term and a radial confinement term; (C) definition of a set of lines ("sticks") connecting these spheres, each associated with a biasing potential involving a one-dimensional longitudinal memory-based term and a transverse confinement term; (D) unification of the biasing potentials corresponding to the union of all of the spheres and lines (active subspace) into a single biasing potential according to the enveloping distribution sampling (EDS) scheme; (E) build-up of the memory using the Local Elevation (LE) procedure, leading to a biasing potential enabling a nearly uniform sampling (radially within the spheres, longitudinally within the lines) of the active subspace; (F) generation of a biased ensemble of configurations using this preoptimized biasing potential, following an umbrella sampling (US) approach; and (G) calculation of the relative free energies of the states via reweighting and state assignment. The main characteristics of this approach are: (i) a low internal dimensionality, that is, the memory only involves one-dimensional grids (acceptable memory requirements); (ii) a minimal irrelevant volume, that is, the conformational volume opened to sampling includes a minimal fraction of irrelevant regions in terms of the free energy of the physical system or of user-specified metastable states (acceptable build-up duration requirements, high statistical efficiency); and (iii) a problem-adapted geometry (a priori specification of the conformational regions considered as relevant or irrelevant). In particular, the use of lines to connect the spheres ensures both a minimal irrelevant volume and a sufficient number of transitions between the states. As an illustration, the BS (ii) a solvated polyalanine decapeptide (nine-dimensional conformational subspace), to evaluate the relative free energies of three different types of helices (π, α, and 310) based on a single simulation; and (iii) a solvated artifical hexopyranose, termed the "mother" of all d-hexopyranoses and constructed as a hybrid of all d-hexopyranose stereoisomers, where the method is applied (seven-dimensional mixed alchemical and conformational subspace) to calculate the relative free energies of the corresponding 32 isomers, anomers, and chair conformers, based on a single simulation.

Halvor S Hansen - One of the best experts on this subject based on the ideXlab platform.

  • Ball-and-Stick Local Elevation Umbrella Sampling: Molecular Simulations Involving Enhanced Sampling within Conformational or Alchemical Subspaces of Low Internal Dimensionalities, Minimal Irrelevant Volumes, and Problem-Adapted Geometries
    Journal of chemical theory and computation, 2010
    Co-Authors: Halvor S Hansen, Philippe H Hunenberger
    Abstract:

    A new method, ball-and-stick Local Elevation umbrella sampling (BS (B) representation of the relevant states by means of spheres ("balls"), each associated with a biasing potential involving a one-dimensional radial memory-based term and a radial confinement term; (C) definition of a set of lines ("sticks") connecting these spheres, each associated with a biasing potential involving a one-dimensional longitudinal memory-based term and a transverse confinement term; (D) unification of the biasing potentials corresponding to the union of all of the spheres and lines (active subspace) into a single biasing potential according to the enveloping distribution sampling (EDS) scheme; (E) build-up of the memory using the Local Elevation (LE) procedure, leading to a biasing potential enabling a nearly uniform sampling (radially within the spheres, longitudinally within the lines) of the active subspace; (F) generation of a biased ensemble of configurations using this preoptimized biasing potential, following an umbrella sampling (US) approach; and (G) calculation of the relative free energies of the states via reweighting and state assignment. The main characteristics of this approach are: (i) a low internal dimensionality, that is, the memory only involves one-dimensional grids (acceptable memory requirements); (ii) a minimal irrelevant volume, that is, the conformational volume opened to sampling includes a minimal fraction of irrelevant regions in terms of the free energy of the physical system or of user-specified metastable states (acceptable build-up duration requirements, high statistical efficiency); and (iii) a problem-adapted geometry (a priori specification of the conformational regions considered as relevant or irrelevant). In particular, the use of lines to connect the spheres ensures both a minimal irrelevant volume and a sufficient number of transitions between the states. As an illustration, the BS (ii) a solvated polyalanine decapeptide (nine-dimensional conformational subspace), to evaluate the relative free energies of three different types of helices (π, α, and 310) based on a single simulation; and (iii) a solvated artifical hexopyranose, termed the "mother" of all d-hexopyranoses and constructed as a hybrid of all d-hexopyranose stereoisomers, where the method is applied (seven-dimensional mixed alchemical and conformational subspace) to calculate the relative free energies of the corresponding 32 isomers, anomers, and chair conformers, based on a single simulation.

  • Enhanced Conformational Sampling in Molecular Dynamics Simulations of Solvated Peptides: Fragment-Based Local Elevation Umbrella Sampling.
    Journal of chemical theory and computation, 2010
    Co-Authors: Halvor S Hansen, Xavier Daura, Philippe H Hunenberger
    Abstract:

    A new method, fragment-based Local Elevation umbrella sampling (FB-LEUS), is proposed to enhance the conformational sampling in explicit-solvent molecular dynamics (MD) simulations of solvated polymers. The method is derived from the Local Elevation umbrella sampling (LEUS) method [ Hansen and Hunenberger , J. Comput. Chem. 2010 , 31 , 1 - 23 ], which combines the Local Elevation (LE) conformational searching and the umbrella sampling (US) conformational sampling approaches into a single scheme. In LEUS, an initial (relatively short) LE build-up (searching) phase is used to construct an optimized (grid-based) biasing potential within a subspace of conformationally relevant degrees of freedom, which is then frozen and used in a (comparatively longer) US sampling phase. This combination dramatically enhances the sampling power of MD simulations but, due to computational and memory costs, is only applicable to relevant subspaces of low dimensionalities. As an attempt to expand the scope of the LEUS approach to solvated polymers with more than a few relevant degrees of freedom, the FB-LEUS scheme involves an US sampling phase that relies on a superposition of low-dimensionality biasing potentials optimized using LEUS at the fragment level. The feasibility of this approach is tested using polyalanine (poly-Ala) and polyvaline (poly-Val) oligopeptides. Two-dimensional biasing potentials are preoptimized at the monopeptide level, and subsequently applied to all dihedral-angle pairs within oligopeptides of 4,  6,  8, or 10 residues. Two types of fragment-based biasing potentials are distinguished: (i) the basin-filling (BF) potentials act so as to "fill" free-energy basins up to a prescribed free-energy level above the global minimum; (ii) the valley-digging (VD) potentials act so as to "dig" valleys between the (four) free-energy minima of the two-dimensional maps, preserving barriers (relative to linearly interpolated free-energy changes) of a prescribed magnitude. The application of these biasing potentials may lead to an impressive enhancement of the searching power (volume of conformational space visited in a given amount of simulation time). However, this increase is largely offset by a deterioration of the statistical efficiency (representativeness of the biased ensemble in terms of the conformational distribution appropriate for the physical ensemble). As a result, it appears difficult to engineer FB-LEUS schemes representing a significant improvement over plain MD, at least for the systems considered here.

  • conformational properties of glucose based disaccharides investigated using molecular dynamics simulations with Local Elevation umbrella sampling
    Carbohydrate Research, 2010
    Co-Authors: Lovorka Perichassler, Halvor S Hansen, Riccardo Baron, Philippe H Hunenberger
    Abstract:

    Abstract Explicit-solvent molecular dynamics (MD) simulations of the 11 glucose-based disaccharides in water at 300 K and 1 bar are reported. The simulations were carried out with the GROMOS 45A4 force-field and the sampling along the glycosidic dihedral angles ϕ and ψ was artificially enhanced using the Local Elevation umbrella sampling (LEUS) method. The trajectories are analyzed in terms of free-energy maps, stable and metastable conformational states (relative free energies and estimated transition timescales), intramolecular H-bonds, single molecule configurational entropies, and agreement with experimental data. All disaccharides considered are found to be characterized either by a single stable (overwhelmingly populated) state ((1→n)-linked disaccharides with n = 1, 2, 3, or 4) or by two stable (comparably populated and differing in the third glycosidic dihedral angle ω ˜ ; gg or gt) states with a low interconversion barrier ((1→6)-linked disaccharides). Metastable (anti-ϕ or anti-ψ) states are also identified with relative free energies in the range of 8–22 kJ mol−1. The 11 compounds can be classified into four families: (i) the α(1→1)α-linked disaccharide trehalose (axial–axial linkage) presents no metastable state, the lowest configurational entropy, and no intramolecular H-bonds; (ii) the four α(1→n)-linked disaccharides (n = 1, 2, 3, or 4; axial–equatorial linkage) present one metastable (anti-ψ) state, an intermediate configurational entropy, and two alternative intramolecular H-bonds; (iii) the four β(1→n)-linked disaccharides (n = 1, 2, 3, or 4; equatorial–equatorial linkage) present two metastable (anti-ϕ and anti-ψ) states, an intermediate configurational entropy, and one intramolecular H-bond; (iv) the two (1→6)-linked disaccharides (additional glycosidic dihedral angle) present no (isomaltose) or a pair of (gentiobiose) metastable (anti-ϕ) states, the highest configurational entropy, and no intramolecular H-bonds. The observed conformational preferences appear to be dictated by four main driving forces (ring conformational preferences, exo-anomeric effect, steric constraints, and possible presence of a third glycosidic dihedral angle), leaving a secondary role to intramolecular H-bonding and specific solvation effects. In spite of the weak conformational driving force attributed to solvent-exposed H-bonds in water (highly polar protic solvent), intramolecular H-bonds may still have a significant influence on the physico-chemical properties of the disaccharide by decreasing its hydrophilicity. Along with previous work, the results also complete the suggestion of a spectrum of approximate transition timescales for carbohydrates up to the disaccharide level, namely: ∼30 ps (hydroxyl groups), ∼1 ns (free lactol group, free hydroxymethyl groups, glycosidic dihedral angle ω ˜ in (1→6)-linked disaccharides), ∼10 ns to 2 μs (ring conformation, glycosidic dihedral angles ϕ and ψ). The calculated average values of the glycosidic torsional angles agree well with the available experimental data, providing validation for the force-field and simulation methodology employed.

  • Conformational properties of glucose-based disaccharides investigated using molecular dynamics simulations with Local Elevation umbrella sampling.
    Carbohydrate research, 2010
    Co-Authors: Lovorka Perić-hassler, Halvor S Hansen, Riccardo Baron, Philippe H Hunenberger
    Abstract:

    Explicit-solvent molecular dynamics (MD) simulations of the 11 glucose-based disaccharides in water at 300K and 1bar are reported. The simulations were carried out with the GROMOS 45A4 force-field and the sampling along the glycosidic dihedral angles phi and psi was artificially enhanced using the Local Elevation umbrella sampling (LEUS) method. The trajectories are analyzed in terms of free-energy maps, stable and metastable conformational states (relative free energies and estimated transition timescales), intramolecular H-bonds, single molecule configurational entropies, and agreement with experimental data. All disaccharides considered are found to be characterized either by a single stable (overwhelmingly populated) state ((1-->n)-linked disaccharides with n=1, 2, 3, or 4) or by two stable (comparably populated and differing in the third glycosidic dihedral angle omega ; gg or gt) states with a low interconversion barrier ((1-->6)-linked disaccharides). Metastable (anti-phi or anti-psi) states are also identified with relative free energies in the range of 8-22 kJ mol(-1). The 11 compounds can be classified into four families: (i) the alpha(1-->1)alpha-linked disaccharide trehalose (axial-axial linkage) presents no metastable state, the lowest configurational entropy, and no intramolecular H-bonds; (ii) the four alpha(1-->n)-linked disaccharides (n=1, 2, 3, or 4; axial-equatorial linkage) present one metastable (anti-psi) state, an intermediate configurational entropy, and two alternative intramolecular H-bonds; (iii) the four beta(1-->n)-linked disaccharides (n=1, 2, 3, or 4; equatorial-equatorial linkage) present two metastable (anti-phi and anti-psi) states, an intermediate configurational entropy, and one intramolecular H-bond; (iv) the two (1-->6)-linked disaccharides (additional glycosidic dihedral angle) present no (isomaltose) or a pair of (gentiobiose) metastable (anti-phi) states, the highest configurational entropy, and no intramolecular H-bonds. The observed conformational preferences appear to be dictated by four main driving forces (ring conformational preferences, exo-anomeric effect, steric constraints, and possible presence of a third glycosidic dihedral angle), leaving a secondary role to intramolecular H-bonding and specific solvation effects. In spite of the weak conformational driving force attributed to solvent-exposed H-bonds in water (highly polar protic solvent), intramolecular H-bonds may still have a significant influence on the physico-chemical properties of the disaccharide by decreasing its hydrophilicity. Along with previous work, the results also complete the suggestion of a spectrum of approximate transition timescales for carbohydrates up to the disaccharide level, namely: approximately 30 ps (hydroxyl groups), approximately 1 ns (free lactol group, free hydroxymethyl groups, glycosidic dihedral angleomega in (1-->6)-linked disaccharides), approximately 10 ns to 2 micros (ring conformation, glycosidic dihedral angles phi and psi). The calculated average values of the glycosidic torsional angles agree well with the available experimental data, providing validation for the force-field and simulation methodology employed.

  • using the Local Elevation method to construct optimized umbrella sampling potentials calculation of the relative free energies and interconversion barriers of glucopyranose ring conformers in water
    Journal of Computational Chemistry, 2010
    Co-Authors: Halvor S Hansen, Philippe H Hunenberger
    Abstract:

    A method is proposed to combine the Local Elevation (LE) conformational searching and the umbrella sampling (US) conformational sampling approaches into a single Local Elevation umbrella sampling (LEUS) scheme for (explicit-solvent) molecular dynamics (MD) simulations. In this approach, an initial (relatively short) LE build-up (searching) phase is used to construct an optimized biasing potential within a subspace of conformationally relevant degrees of freedom, that is then used in a (comparatively longer) US sampling phase. This scheme dramatically enhances (in comparison with plain MD) the sampling power of MD simulations, taking advantage of the fact that the preoptimized biasing potential represents a reasonable approximation to the negative of the free energy surface in the considered conformational subspace. The method is applied to the calculation of the relative free energies of β-D-glucopyranose ring conformers in water (within the GROMOS 45A4 force field). Different schemes to assign sampled conformational regions to distinct states are also compared. This approach, which bears some analogies with adaptive umbrella sampling and metadynamics (but within a very distinct implementation), is shown to be: (i) efficient (nearly all the computational effort is invested in the actual sampling phase rather than in searching and equilibration); (ii) robust (the method is only weakly sensitive to the details of the build-up protocol, even for relatively short build-up times); (iii) versatile (a LEUS biasing potential database could easily be preoptimized for small molecules and assembled on a fragment basis for larger ones). © 2009 Wiley Periodicals, Inc. J Comput Chem 2010

Noah S. Bieler - One of the best experts on this subject based on the ideXlab platform.

  • Multistate λ-Local-Elevation umbrella-sampling (MS-λ-LEUS): method and application to the complexation of cations by crown ethers.
    Journal of chemical theory and computation, 2015
    Co-Authors: Noah S. Bieler, Jan P Tschopp, Philippe H Hunenberger
    Abstract:

    An extension of the λ-Local-Elevation umbrella-sampling (λ-LEUS) scheme [ Bieler et al. J. Chem. Theory Comput. 2014 , 10 , 3006 ] is proposed to handle the multistate (MS) situation, i.e. the calculation of the relative free energies of multiple physical states based on a single simulation. The key element of the MS-λ-LEUS approach is to use a single coupling variable Λ controlling successive pairwise mutations between the states of interest in a cyclic fashion. The Λ variable is propagated dynamically as an extended-system variable, using a coordinate transformation with plateaus and a memory-based biasing potential as in λ-LEUS. Compared to other available MS schemes (one-step perturbation, enveloping distribution sampling and conventional λ-dynamics) the proposed method presents a number of important advantages, namely: (i) the physical states are visited explicitly and over finite time periods; (ii) the extent of unphysical space required to ensure transitions is kept minimal and, in particular, one-dimensional; (iii) the setup protocol solely requires the topologies of the physical states; and (iv) the method only requires limited modifications in a simulation code capable of handling two-state mutations. As an initial application, the absolute binding free energies of five alkali cations to three crown ethers in three different solvents are calculated. The results are found to reproduce qualitatively the main experimental trends and, in particular, the experimental selectivity of 18C6 for K(+) in water and methanol, which is interpreted in terms of opposing trends along the cation series between the solvation free energy of the cation and the direct electrostatic interactions within the complex.

  • Communication: estimating the initial biasing potential for λ-Local-Elevation umbrella-sampling (λ-LEUS) simulations via slow growth.
    The Journal of chemical physics, 2014
    Co-Authors: Noah S. Bieler, Philippe H Hunenberger
    Abstract:

    In a recent article [Bieler et al. , J. Chem. Theory Comput.10, 3006–3022 (2014)], we introduced a combination of the λ-dynamics (λD) approach for calculating alchemical free-energy differences and of the Local-Elevation umbrella-sampling (LEUS) memory-based biasing method to enhance the sampling along the alchemical coordinate. The combined scheme, referred to as λ-LEUS, was applied to the perturbation of hydroquinone to benzene in water as a test system, and found to represent an improvement over thermodynamic integration (TI) in terms of sampling efficiency at equivalent accuracy. However, the preoptimization of the biasing potential required in the λ-LEUS method requires “filling up” all the basins in the potential of mean force. This introduces a non-productive pre-sampling time that is system-dependent, and generally exceeds the corresponding equilibration time in a TI calculation. In this letter, a remedy is proposed to this problem, termed the slow growth memory guessing (SGMG) approach. Instead of initializing the biasing potential to zero at the start of the preoptimization, an approximate potential of mean force is estimated from a short slow growth calculation, and its negative used to construct the initial memory. Considering the same test system as in the preceding article, it is shown that of the application of SGMG in λ-LEUS permits to reduce the preoptimization time by about a factor of four.

  • Local Elevation Umbrella Sampling Applied to the Calculation of Alchemical Free-Energy Changes via λ-Dynamics: The λ-LEUS Scheme.
    Journal of chemical theory and computation, 2014
    Co-Authors: Noah S. Bieler, Rico Häuselmann, Philippe H Hunenberger
    Abstract:

    When using molecular dynamics (MD) simulations for the calculation of alchemical free-energy changes, the extended-dynamics method called λ-dynamics (λD) in its currently available implementations does not compare very favorably with thermodynamic integration (TI) in terms of robustness, efficiency, and accuracy, although it is in principle easier to set up, postprocess, and automatize. In the present article, the main shortcomings of the λD approach are carefully analyzed, and possible remedies are proposed. The resulting scheme, called λ-LEUS, involves: (i) the use of a simple noninvertible coordinate transformation ensuring a finite sampling of the two physical end states; (ii) the application of the Local Elevation umbrella sampling (LEUS) memory-based biasing scheme to enforce homogeneous sampling and overcome barriers along the alchemical coordinate; (iii) recommendations concerning the choice of the mass parameter and of the temperature-coupling scheme for this coordinate; (iv) the use of a second-order splines basis set for the memory-based biasing functions. The λ-LEUS scheme is described and tested considering the perturbation of hydroquinone to benzene in water. The results are compared to those of TI calculations and exhibit a superior accuracy-to-efficiency ratio, presumably because dynamic variations in the alchemical coordinate open up pathways to circumvent orthogonal barriers, these pathways being inaccessible when the coordinate is constrained. Therefore, λ-LEUS combines the practical advantages of λD with the robustness of TI, simultaneously affording a slightly enhanced computational efficiency.

Shigeatsu Endo - One of the best experts on this subject based on the ideXlab platform.

  • Local Elevation of the anti-inflammatory interleukin-10 in the pathogenesis of chronic subdural hematoma
    Neurosurgical review, 2006
    Co-Authors: Tsukasa Wada, Kiyoshi Kuroda, Yuki Yoshida, Kuniaki Ogasawara, Akira Ogawa, Shigeatsu Endo
    Abstract:

    We investigated the relationship between inflammatory and anti-inflammatory cytokines in the pathogenesis of chronic subdural hematoma (CSDH) by measuring the plasma and subdural fluid levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). The levels of IL-6, IL-8 and IL-10 were measured in the subdural fluid obtained from 34 patients with CSDH, using the enzyme-linked immunosorbent assay. The patients were classified into a high IL-10 group and a low IL-10 group according to the level of IL-10 in their subdural fluid samples. The subdural fluid levels of IL-6 and IL-8 were significantly higher in the high IL-10 group than in the low IL-10 group (P

  • Local Elevation of the anti inflammatory interleukin 10 in the pathogenesis of chronic subdural hematoma
    Neurosurgical Review, 2006
    Co-Authors: Tsukasa Wada, Kiyoshi Kuroda, Yuki Yoshida, Kuniaki Ogasawara, Akira Ogawa, Shigeatsu Endo
    Abstract:

    We investigated the relationship between inflammatory and anti-inflammatory cytokines in the pathogenesis of chronic subdural hematoma (CSDH) by measuring the plasma and subdural fluid levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). The levels of IL-6, IL-8 and IL-10 were measured in the subdural fluid obtained from 34 patients with CSDH, using the enzyme-linked immunosorbent assay. The patients were classified into a high IL-10 group and a low IL-10 group according to the level of IL-10 in their subdural fluid samples. The subdural fluid levels of IL-6 and IL-8 were significantly higher in the high IL-10 group than in the low IL-10 group (P<0.05). A tendency for the patients in the low IL-10 group to show the separated or layer type of pattern on the CT scans was noted.

Tsukasa Wada - One of the best experts on this subject based on the ideXlab platform.

  • Local Elevation of the anti-inflammatory interleukin-10 in the pathogenesis of chronic subdural hematoma
    Neurosurgical review, 2006
    Co-Authors: Tsukasa Wada, Kiyoshi Kuroda, Yuki Yoshida, Kuniaki Ogasawara, Akira Ogawa, Shigeatsu Endo
    Abstract:

    We investigated the relationship between inflammatory and anti-inflammatory cytokines in the pathogenesis of chronic subdural hematoma (CSDH) by measuring the plasma and subdural fluid levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). The levels of IL-6, IL-8 and IL-10 were measured in the subdural fluid obtained from 34 patients with CSDH, using the enzyme-linked immunosorbent assay. The patients were classified into a high IL-10 group and a low IL-10 group according to the level of IL-10 in their subdural fluid samples. The subdural fluid levels of IL-6 and IL-8 were significantly higher in the high IL-10 group than in the low IL-10 group (P

  • Local Elevation of the anti inflammatory interleukin 10 in the pathogenesis of chronic subdural hematoma
    Neurosurgical Review, 2006
    Co-Authors: Tsukasa Wada, Kiyoshi Kuroda, Yuki Yoshida, Kuniaki Ogasawara, Akira Ogawa, Shigeatsu Endo
    Abstract:

    We investigated the relationship between inflammatory and anti-inflammatory cytokines in the pathogenesis of chronic subdural hematoma (CSDH) by measuring the plasma and subdural fluid levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). The levels of IL-6, IL-8 and IL-10 were measured in the subdural fluid obtained from 34 patients with CSDH, using the enzyme-linked immunosorbent assay. The patients were classified into a high IL-10 group and a low IL-10 group according to the level of IL-10 in their subdural fluid samples. The subdural fluid levels of IL-6 and IL-8 were significantly higher in the high IL-10 group than in the low IL-10 group (P<0.05). A tendency for the patients in the low IL-10 group to show the separated or layer type of pattern on the CT scans was noted.