Development of Surface-SFED Models for Polar Solvents

Lee, Se-Han; Cho, Kwang Hwi; Acree, William E.; No, Kyoung Tai

doi:10.1021/ci2004913

Cited by 9 publications

(17 citation statements)

References 38 publications

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“…The model can provide reliable salvation free energies of experimentally unavailable solute-solvent pairs. Previously, we demonstrated that the solvation free energy density (SFED) model is an efficient one for the description of molecular properties in solution with a linear combination of empirical functions of the solute properties (45)(46)(47)(48)(49)(50). However, the parameterization of the linear expansion coefficients, optimized for each solvent, limits the application of the model to solvents for which the coefficients were determined.…”

Section: Significancementioning

confidence: 99%

“…Here we present the generalized SFED (G-SFED) model to calculate the solvation free energies of a molecule including biological molecules in any environment. The effects of the solute on various solute-solvent interactions are represented by the basis functions developed earlier (46)(47)(48)(49)(50), and the complementary solvent effects on these interactions are reflected in the coefficients with a few solvent properties.…”

Section: Significancementioning

confidence: 99%

“…To describe ΔG inter , which originates from the phenomena described above, previous work (45)(46)(47)(48)(49)(50) …”

Section: Theorymentioning

confidence: 99%

“…This set encompassed a broad range of common functional groups present in biological and drugable small molecules that possess H, C, N, O, F, S, Cl, Br, and I atoms. The data set for validation of the model is taken from our previous work (50). After exclusion of data in common with the training set, the external validation set consisted of 3,580 unique solvation free energies of 741 neutral molecules in 36 polar solvents.…”

Section: Theorymentioning

confidence: 99%

“…The parameters for calculating q i and α i of the solute and those describing the cavity surface were taken from our previous work (46)(47)(48)(49)(50)(51)(52)(53)(54)(55), and only 12 empirical parameters were determined by minimizing the difference between calculated (ΔG cal solv ) and experimental (ΔG exp solv ) solvation free energies. The optimized 12 empirical parameters and the contribution of each basis function to ΔG solv are given in Table 1 and Table S2.…”

Section: Theorymentioning

confidence: 99%

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A generalized G-SFED continuum solvation free energy calculation model

Lee

Cho

Kang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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An empirical continuum solvation model, solvation free energy density (SFED), has been developed to calculate solvation free energies of a molecule in the most frequently used solvents. A generalized version of the SFED model, generalized-SFED (G-SFED), is proposed here to calculate molecular solvation free energies in virtually any solvent. G-SFED provides an accurate and fast generalized framework without a complicated description of a solution. In the model, the solvation free energy of a solute is represented as a linear combination of empirical functions of the solute properties representing the effects of solute on various solute-solvent interactions, and the complementary solvent effects on these interactions were reflected in the linear expansion coefficients with a few solvent properties. G-SFED works well for a wide range of sizes and polarities of solute molecules in various solvents as shown by a set of 5,753 solvation free energies of diverse combinations of 103 solvents and 890 solutes. Octanol-water partition coefficients of small organic compounds and peptides were calculated with G-SFED with accuracy within 0.4 log unit for each group. The G-SFED computation time depends linearly on the number of nonhydrogen atoms (n) in a molecule, O(n).implicit solvent | macromolecules | linear time A n accurate description of the effect of solvent on solvation is crucial for understanding chemical and biological phenomena. Because many peptide and protein drugs are currently being developed (1, 2), computational efficiency as well as accuracy are very important. Among the different approaches that have been used, continuum solvation models are appealing because of the simplified yet accurate description of the solvent effect (3-8).Continuum solvent models have been developed based on the early work of Born (9), Bell (10), Kirkwood (11), and Onsanger (12). They focus primarily on the description of the solute either at the quantum mechanical level or as a classical collection of point charges and try to represent the influence of the solvent based on an approximate treatment as a dielectric continuum medium. The charge distribution of the solute induces electric polarization of the surrounding solvent, and the electric field generated by the polarized solvent, the reaction field, in turn perturbs the solute, leading to a modification of the charge distribution of the solute. This electrostatic problem of the mutual polarization between solute and solvent can be recast by using boundary conditions at the cavity surface, leading to significant simplifications in the associated equations.In the classical approaches, most work is concerned with describing the electrostatic contribution to the solvation in terms of the Poisson-Boltzmann equation (PBE) (13). Several different computational techniques for solving the PBE have been developed, for example, finite difference methods in which the dielectric property of the solvent is described in terms of a 3D grid around the solute (14-17) and boundary element methods i...

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Section: Significancementioning

confidence: 99%

Section: Significancementioning

confidence: 99%

“…To describe ΔG inter , which originates from the phenomena described above, previous work (45)(46)(47)(48)(49)(50) …”

Section: Theorymentioning

confidence: 99%

Section: Theorymentioning

confidence: 99%

Section: Theorymentioning

confidence: 99%

See 3 more Smart Citations

A generalized G-SFED continuum solvation free energy calculation model

Lee

Cho

Kang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Comparative assessment of computational methods for the determination of solvation free energies in alcohol‐based molecules

Martins

Sousa

2013

J Comput Chem

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The determination of differences in solvation free energies between related drug molecules remains an important challenge in computational drug optimization, when fast and accurate calculation of differences in binding free energy are required. In this study, we have evaluated the performance of five commonly used polarized continuum model (PCM) methodologies in the determination of solvation free energies for 53 typical alcohol and alkane small molecules. In addition, the performance of these PCM methods, of a thermodynamic integration (TI) protocol and of the Poisson-Boltzmann (PB) and generalized Born (GB) methods, were tested in the determination of solvation free energies changes for 28 common alkane-alcohol transformations, by the substitution of an hydrogen atom for a hydroxyl substituent. The results show that the solvation model D (SMD) performs better among the PCM-based approaches in estimating solvation free energies for alcohol molecules, and solvation free energy changes for alkane-alcohol transformations, with an average error below 1 kcal/mol for both quantities. However, for the determination of solvation free energy changes on alkane-alcohol transformation, PB and TI yielded better results. TI was particularly accurate in the treatment of hydroxyl groups additions to aromatic rings (0.53 kcal/mol), a common transformation when optimizing drug-binding in computer-aided drug design.

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