Applicability of a continuum solvation model to the octanol water transfer: CFF91 based model for amino acids

Schmidt, A.B.; Fine, Richard M.

doi:10.1002/bip.360360505

Cited by 6 publications

(9 citation statements)

References 36 publications

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“…Flory−Huggins theory is a BIPSE model that treats polymer conformational changes; QSAR (Quantitative Structure−Activity Relationships) are BIPSE models that are used to predict drug interactions with proteins . BIPSE models have been used to treat protein folding, micelle formation, docking, chromatographic retention, solvation, and other processes. ,,− …”

Section: Bipse: Modeling Biomolecule Folding Docking and Partitionin...mentioning

confidence: 99%

A View of the Hydrophobic Effect

2001

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Oil and water do not mix. The disaffinity of oil for water, with its unusual temperature dependence, is called the hydrophobic effect. It is important to understand the factors underlying the hydrophobic effect because they appear to play key roles in membrane and micelle formation, protein folding, ligand-protein and proteinprotein binding, chromatographic retention, possibly nucleic acid interactions, and the partitioning of drugs, metabolites, and toxins throughout the environment and living systems. Here, we survey experimental and theoretical studies of nonpolar solute partitioning into water. We note that the hydrophobic effect is not just due to "water ordering" and not merely due to small size effects of water. The properties vary substantially with temperature and solute shape. Also, we discuss the limitations of using oil/water partitioning as the basis for some thermodynamic models in chemistry and biology. † Graduate Group in Biophysics.

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Section: Bipse: Modeling Biomolecule Folding Docking and Partitionin...mentioning

confidence: 99%

A View of the Hydrophobic Effect

2001

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“…30 Monte Carlo (MC) simulations were performed for the log P, 31 and a continuum Poisson-Boltzmann hydration model has been extended to the octanol-water transfer. 32 A general stochastic algorithm based on the simulated annealing method was applied to search for structures having low log P. 33 MD free energy perturbation (FEP) simulations were carried out to estimate the relative log P and compared to GB/SA octanol continuum solvation model 34 . Chen and Siepmann have used Gibbs ensemble Monte Carlo simulations to calculate partitioning of short alkanes and alcohols between water, octanol, and a gsa phase.…”

Section: Introductionmentioning

confidence: 99%

“…MD simulations were also carried out to analyze octanol/water solvation-shell structuring around the solutes to gain insight into hydrated 1-octanol's capability to serve as a biophase analog . Monte Carlo (MC) simulations were performed for the log P, and a continuum Poisson−Boltzmann hydration model has been extended to the octanol−water transfer . A general stochastic algorithm based on the simulated annealing method was applied to search for structures having low log P .…”

Section: Introductionmentioning

confidence: 99%

Solubility of Organic Compounds in Water/Octanol Systems. A Expanded Ensemble Molecular Dynamics Simulation Study of logPParameters

et al. 2001

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The expanded ensemble method, developed to calculate solvation free energies, is applied to calculate octanol/ water partition coefficients P for some organic drug-related molecules and compared with experimental results. The experimental log P results were obtained by a miniaturized vial procedure using liquid chromatography with UV for quantification. The expanded ensemble technique, implemented within molecular dynamics scheme, is adapted to treat molecules of arbitrary size and type. For octanol, both all-atom and united atom models are evaluated. The solvation free energy of the organic solute molecules is found to be sensitive to the used sets of partial charges on the atoms in polar groups, particularly in water but also in the saturated octanol phase. Although this effect partially cancels out in the calculated partition coefficients, the charges obtained from ab initio Mulliken population analysis give consistently larger log P values than those obtained in simulations with the larger empirical atomic charges included in the CHARMM force field. In general, calculated log P turned out to be systematically higher than those measured experimentally. The possibility of improving potential models for the solutes in water and oil phase, respectively, is discussed.

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“…5 Sometimes the solute-excluded volume is used instead of the solute surface area. 6 This numerical method is adjusted to give reasonable results but costs computational time. It is not clear at all whether this macroscopic model can be employed to microscopic solute molecular systems; e.g., solvent saturation effects are neglected.…”

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confidence: 99%

“…This can lead to problems with the solvent dielectric constant, which are obvious in the paper by Schmidt and Fine. 6 They have to use a dielectric constant for octanol of 3, although the experimental value is 10.3. The generalized Born/surface area model 7 is also applicable and used for these types of problems.…”

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confidence: 99%

Calculated Solvation Free Energies of Amino Acids in a Dipolar Approximation

Sandberg

Edholm

2000

J. Phys. Chem. B

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The solvation free energies of amino acids (hydrophobicities) are rationalized here by using a simple electrostatic ab initio model. The parameters of the model are the surface energy density (γ = 9.55 kJ/mol/nm2, the same for all atoms), the fractional charges, and the radii of the atoms of the amino acids. From the fractional charges, dipoles are constructed, and the polarization energies (self-energies) of the dipoles are calculated. The saturation effect of the solvent is included in the model. The dipole electrostatic contribution is in general not very sensitive to the choice of parameters. In contrast, the self-energies of single net charges are extremely sensitive to the choice of the Born radius. However, for amino acids that may carry a net charge, this energy will be prohibitively large in a low-dielectric medium. Therefore, they will in general change their protonation state to become neutral. The energetic cost of this is calculated from the difference between the amino acid side chain pK a's and the pH of the solvent. This results in a hydrophobicity scale for amino acid side chains based on fundamendal physics that agrees well with experimental hydrophobicity scales. The solvation energy for the amino acid backbone (the peptide bond) can also be calculated in this way. This gives good agreement with available experimental data.

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Applicability of a continuum solvation model to the octanol water transfer: CFF91 based model for amino acids

Cited by 6 publications

References 36 publications

A View of the Hydrophobic Effect

A View of the Hydrophobic Effect

Solubility of Organic Compounds in Water/Octanol Systems. A Expanded Ensemble Molecular Dynamics Simulation Study of logPParameters

Calculated Solvation Free Energies of Amino Acids in a Dipolar Approximation

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