COSMO-RS for aqueous solvation and interfaces

Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals solvent structures and preferential interaction sites (hot spots) on the protein surface. The information provided by water and its cosolvents can be used very effectively to understand protein ligand recognition and to improve the predictive capability of well-established methods such as molecular docking. The application of MD simulations to the study of the association of proteins with drug-like compounds is currently only possible for specific cases, as it remains computationally very expensive and labor intensive. MDmix simulations on the other hand, can be used systematically to address some of the common tasks in SBDD. With the advent of new tools and faster computers we expect to see an increase in the application of mixed solvent MD simulations to a plethora of protein targets to identify new drug candidates.

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Isotope effects in aqueous solvation of simple halides

The Journal of Chemical Physics ◽

10.1063/1.4986231 ◽

2018 ◽

Vol 148 (10) ◽

pp. 102306 ◽

Cited By ~ 6

Author(s):

Pablo E. Videla ◽

Peter J. Rossky ◽

D. Laria

Keyword(s):

Isotope Effects ◽

Aqueous Solvation

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The Aqueous Solvation of Water: A Comparison of Continuum Methods with Molecular Dynamics

Journal of the American Chemical Society ◽

10.1021/ja00088a034 ◽

1994 ◽

Vol 116 (9) ◽

pp. 3949-3954 ◽

Cited By ~ 76

Author(s):

Steven W. Rick ◽

B. J. Berne

Keyword(s):

Molecular Dynamics ◽

Aqueous Solvation

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Improving Solvation Energy Predictions Using The SMD Solvation Method and Semiempirical Electronic Structure Methods

10.26434/chemrxiv.6708554.v1 ◽

2018 ◽

Author(s):

Jimmy C. Kromann ◽

Casper Steinmann ◽

Jan Halborg Jensen

Keyword(s):

Continuum Model ◽

Solvation Energy ◽

Solvation Model ◽

Polar Solvents ◽

Data Set ◽

Solvation Energies ◽

Polarized Continuum Model ◽

Electronic Structure Methods ◽

Aqueous Solvation ◽

Model C

The PM6 implementation in the GAMESS program is extended to elements requiring d-integrals and interfaced with the conducter-like polarized continuum model (C-PCM) of solvation, in- cluding gradients. The accuracy of aqueous solvation energies computed using AM1, PM3, PM6, and DFTB and the SMD continuum solvation model is tested using the MNSOL data set. The errors in SMD solvation energies predicted using NDDO-based methods is considerably larger than when using DFT and HF, with RMSE values of 3.4-5.9 (neutrals) and 6-15 kcal/mol (ions) compared to 2.4 and ca 5 kcal/mol for HF/6-31G(d). For the NDDO-based methods the errors are especially large for cations and considerably higher than the corresponding COSMO results, which suggests that the NDDO/SMD results can be improved by re-parameterizing the SMD parameters focusing on ions. We found the best results are obtained by changing only the radii for hydrogen, carbon, oxygen, nitrogen, and sulfur and this leads to RMSE values for PM3 (neutrals: 2.8/ions: ca 5 kcal/mol), PM6 (4.7/ca 5 kcal/mol), and DFTB (3.9/ca 5 kcal/mol) that are more comparable to HF/6-31G(d) (2.4/ca 5 kcal/mol). Though the radii are optimized to reproduce aqueous solvation energies, they also lead more accurate predictions for other polar solvents such as DMSO, acetonitrile, and methanol, while the improvements for non-polar solvents are negligible.

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