Accelerated Poisson–Boltzmann calculations for static and dynamic systems

Luo, Ray; David, Laurent; Gilson, Michael K.

doi:10.1002/jcc.10120

Cited by 434 publications

(502 citation statements)

References 92 publications

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“…Although this model represents an approximation at a fundamental level, it has in many cases been successful in calculating various macromolecular properties. [1][2][3][4][5][6][7] The continuum models have several advantages over the explicit water representation, especially in molecular dynamics (MD) simulations:…”

Section: Introductionmentioning

confidence: 99%

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

2004

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Implicit solvation models provide, for many applications, a reasonably accurate and computationally effective way to describe the electrostatics of aqueous solvation. Here, a popular analytical Generalized Born (GB) solvation model is modified to improve its accuracy in calculating the solvent polarization part of free energy changes in large-scale conformational transitions, such as protein folding. In contrast to an earlier GB model (implemented in the AMBER-6 program), the improved version does not overstabilize the native structures relative to the finite-difference PoissonBoltzmann continuum treatment. In addition to improving the energy balance between folded and unfolded conformers, the algorithm (available in the AMBER-7 and NAB molecular modeling packages) is shown to perform well in more than 50 ns of native-state molecular dynamics (MD) simulations of thioredoxin, protein-A, and ubiquitin, as well as in a simulation of Barnase/Barstar complex formation. For thioredoxin, various combinations of input parameters have been explored, such as the underlying gas-phase force fields and the atomic radii. The best performance is achieved with a previously proposed modification to the torsional potential in the Amber ff99 force field, which yields stable native trajectories for all of the tested proteins, with backbone root-mean-square deviations from the native structures being ϳ1.5 Å after 6 ns of simulation time. The structure of Barnase/Barstar complex is regenerated, starting from an unbound state, to within 1.9 Å relative to the crystal structure of the complex.

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Section: Introductionmentioning

confidence: 99%

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

2004

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“…Although the PB equation may be solved numerically and can be applied to heterogeneous environments, [16][17][18][19][20] it is generally difficult to balance efficiency and accuracy in direct solutions to the PB equation for the purpose of molecular dynamics simulations. [21][22][23][24] The generalized Born (GB) model offers an efficient analytical approximation to the electrostatic solvation free energy of a solute in aqueous solution according to PB theory. 25 A number of GB variants have been proposed in recent years that are summarized in a recent review.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulations of Large Integral Membrane Proteins with an Implicit Membrane Model

Tanizaki

Feig

2005

J. Phys. Chem. B

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The heterogeneous dielectric generalized Born (HDGB) methodology is an the extension of the GBMV model for the simulation of integral membrane proteins with an implicit membrane environment. Three large integral membrane proteins, the bacteriorhodopsin monomer and trimer and the BtuCD protein, were simulated with the HDGB model in order to evaluate how well thermodynamic and dynamic properties are reproduced. Effects of the truncation of electrostatic interactions were examined. For all proteins, the HDGB model was able to generate stable trajectories that remained close to the starting experimental structures, in excellent agreement with explicit membrane simulations. Dynamic properties evaluated through a comparison of B-factors are also in good agreement with experiment and explicit membrane simulations. However, overall flexibility was slightly underestimated with the HDGB model unless a very large electrostatic cutoff is employed. Results with the HDGB model are further compared with equivalent simulations in implicit aqueous solvent, demonstrating that the membrane environment leads to more realistic simulations.

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“…[2][3][4] Reliable models of hydration are therefore needed if one aims to predict thermodynamic driving forces or to make predictions that will be useful in drug design and protein engineering. [5][6][7][8][9][10] Widely used implicit solvation models based on continuum dielectric theory, e.g., the PoissonBoltzmann (PB) [11][12][13][14] and Generalized Born (GB) [15][16][17][18][19][20] models, provide rapid estimates of the polar solvation free energy, a large portion of total solvation free energy of a polar molecule in water, at lower computational cost than explicit solvent models. Such models can be combined with additional terms to account for nonpolar contributions to the solvation free energy.…”

Section: Introductionmentioning

confidence: 99%

The electrostatic response of water to neutral polar solutes: Implications for continuum solvent modeling

Muddana

Sapra

Fenley

et al. 2013

The Journal of Chemical Physics

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Continuum solvation models are widely used to estimate the hydration free energies of small molecules and proteins, in applications ranging from drug design to protein engineering, and most such models are based on the approximation of a linear dielectric response by the solvent. We used explicit-water molecular dynamics simulations with the TIP3P water model to probe this linear response approximation in the case of neutral polar molecules, using miniature cucurbituril and cyclodextrin receptors and protein side-chain analogs as model systems. We observe supralinear electrostatic solvent responses, and this nonlinearity is found to result primarily from waters' being drawn closer and closer to the solutes with increased solute-solvent electrostatic interactions; i.e., from solute electrostriction. Dielectric saturation and changes in the water-water hydrogen bonding network, on the other hand, play little role. Thus, accounting for solute electrostriction may be a productive approach to improving the accuracy of continuum solvation models. © 2013 AIP Publishing LLC.

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Accelerated Poisson–Boltzmann calculations for static and dynamic systems

Cited by 434 publications

References 92 publications

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

Molecular Dynamics Simulations of Large Integral Membrane Proteins with an Implicit Membrane Model

The electrostatic response of water to neutral polar solutes: Implications for continuum solvent modeling

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