A smooth permittivity function for Poisson–Boltzmann solvation methods

Grant, J. Andrew; Pickup, Barry T.; Nicholls, Anthony

doi:10.1002/jcc.1032.abs

Cited by 96 publications

(171 citation statements)

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“…1. In particular, such a function accounts for the ionic interactions being based on a combination of surface contact terms and Poisson–Boltzmann energy approximations (as computed by ZAP module) 29 …”

Section: Resultsmentioning

confidence: 99%

Modeling of the Intestinal Peptide Transporter hPepT1 and Analysis of Its Transport Capacities by Docking and Pharmacophore Mapping

et al. 2008

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Homology model for hPepT1The Figure shows the hPepT1 model, colored by segments, unveiling its typical folding with 12 transmembrane segments (TM1-12) and a large extracellular loop (EL5). The structural quality of the model is assessed by the significant percentage of residues which fall in the allowed regions of the Ramachandran's plot (70.62%) with a marked preponderance of helix motifs.The TM bundle assumes an elliptical truncated conic shape, which is due to fact that the TM segments are far from being parallel and some segments are staggered with an angle of 30°in respect to the adjacent heli ces. The TMs arrangement does not agree the numerical order, but it is possible to recognize an internal group of helices (i.e. TM1, TM4, TM5, TM7, TM10), which line the central pore and bear the key residues for the binding, and an external set of TM segments (TM2, TM3, TM6, TM8, TM11, TM12), which define the boundary of TM bundle. Notably, the helices facing the central pore are clearly more hydrophilic than the external TM segments.The extracellular loop EL5 (red segment) fully covers the extracellular side and consists of two large domains connected by two hinge loops. The hinges may confer flexibility to the domains, which could assume closed or open conformations modulating the accessibility of the binding cavity. Such a flexibility is confirmed by the used template (sucrose phosphatase) which can assume two different states. Such template is a metalloenzyme which selectively recognizes some sugars. This suggests that also EL5 may bind sugars and/or metal ions involved in modulatory effects on hPePT1, as reported by experimental studies. Docking analysesAsn22 Glu23 Ile331 Trp294Phe293 Trp294 Glu291 Thr327The ammonium head probably plays the most critical role since it realizes a reinforced Hbond with Tyr588 as well as ion-pairs with Glu23 (TM1) and/or Glu26 (TM1).Notably, the contact between Tyr588 and ammonium head characterizes the most affinitive ligands.The carboxy terminus appears less involved in ligand recognition, since it stabilizes only H-bonds with the backbone of Ala295 (TM7), Leu296 (TM7), and Phe297 (TM7) without forming strong ionic interactionsThe residues which interact with the side chains are heterogeneous, justifying the ability of hPepT1 to interact with structurally diverse substrates. It is possible to recognize a set of residues involved in the interaction with the N-terminal side chain (SC1) such as Asn22 (TM1), Glu23, and Phe293, while the Cterminal side chain (SC2) contact Trp294, Ile331 (TM8), and Glu291 (TM7) and Thr327 (EL4).The central peptide bond can stabilize H-bonds with backbone atoms of Phe293 and Trp294. Such interactions can be hindered by bulky side chains, and, thus, one can conclude that the contacts of the peptide groups could partially counterbalance the reduced interactions stabilized by small side chains.

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Section: Resultsmentioning

confidence: 99%

Modeling of the Intestinal Peptide Transporter hPepT1 and Analysis of Its Transport Capacities by Docking and Pharmacophore Mapping

et al. 2008

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“…Parallel to the experimental studies, several theoretical and computational models have been developed to quantify the ion effects of DNA bending and the persistence length based on the Debye-Hückel (DH) theory (25)(26)(27), the counterion condensation (CC) theory (28)(29)(30)(31), the (cylindrical) Poisson-Boltzmann (PB) theory (32,33), and the discrete-charge interaction model (34)(35)(36). The existing theories, including the DH, CC, and PB theories, have been quite successful in predicting the electrostatics of nucleic acids and proteins (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). However, most theories either use simplified models for DNA structure such as the uniform cylinder and the linecharge models or ignore the added salt in the supporting solution.…”

Section: Introductionmentioning

confidence: 99%

“…The CC theory is based on the assumption of two-state ion distribution and is a double-limit law, i.e., it is developed for dilute salt solution and nucleic acids of infinite length (28). The PB theory is a mean-field theory (37)(38)(39)(40)(41)(42)(43)(44). It ignores ion-ion correlations which can be important for multivalent ions, e.g., Mg 21 (45)(46)(47)(48)(49)(50)(51).…”

Section: Introductionmentioning

confidence: 99%

Electrostatic Free Energy Landscapes for DNA Helix Bending

Tan

Chen

2008

Biophysical Journal

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Nucleic acids are highly charged polyanionic molecules; thus, the ionic conditions are crucial for nucleic acid structural changes such as bending. We use the tightly bound ion theory, which explicitly accounts for the correlation and ensemble effects for counterions, to calculate the electrostatic free energy landscapes for DNA helix bending. The electrostatic free energy landscapes show that DNA bending energy is strongly dependent on ion concentration, valency, and size. In a Na(+) solution, DNA bending is electrostatically unfavorable because of the strong charge repulsion on backbone. With the increase of the Na(+) concentration, the electrostatic bending repulsion is reduced and thus the bending becomes less unfavorable. In contrast, in an Mg(2+) solution, ion correlation induces a possible attractive force between the different parts of the helical strands, resulting in bending. The electrostatically most favorable and unfavorable bending directions are toward the major and minor grooves, respectively. Decreasing the size of the divalent ions enhances the electrostatic bending attraction, causing an increased bending angle, and shifts the most favorable bending to the direction toward the minor groove. The microscopic analysis on ion-binding distribution reveals that the divalent ion-induced helix bending attraction may come from the correlated distribution of the ions across the grooves in the bending direction.

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“…Because the solute–solvent interface is more complicated than a simple surface made of interlocking spheres, there is indeed no reason to limit the model to a sharp solute–solvent transition. In the context of classic molecular dynamics simulations, smooth dielectric models have also been proposed to avoid discontinuities in the reaction field forces 11–13.…”

Section: Introductionmentioning

confidence: 99%

First‐principles molecular dynamics simulations in a continuum solvent

Fattebert¹,

Gygi²

2003

Int J of Quantum Chemistry

136

189

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ABSTRACT:A new continuum solvation model for density functional theory firstprinciples simulations is presented in the context of plane wave Car-Parrinello molecular dynamics. The Poisson problem-with dielectric function representing the solvent effects-is solved by a compact finite difference method on a regular grid. The smoothness of the solute-solvent transition, and the density-based solute cavity, provide good numerical properties to the model and allow for total energy calculations, reaction barriers calculations, and energy-conserving molecular dynamics.

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A smooth permittivity function for Poisson–Boltzmann solvation methods

Cited by 96 publications

References 0 publications

Modeling of the Intestinal Peptide Transporter hPepT1 and Analysis of Its Transport Capacities by Docking and Pharmacophore Mapping

Modeling of the Intestinal Peptide Transporter hPepT1 and Analysis of Its Transport Capacities by Docking and Pharmacophore Mapping

Electrostatic Free Energy Landscapes for DNA Helix Bending

First‐principles molecular dynamics simulations in a continuum solvent

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