Artículo
Predicting octanol/water partition coefficients and pKa for the SAMPL7 challenge using the SM12, SM8 and SMD solvation models
Fecha de publicación:
09/2022
Editorial:
Springer
Revista:
Journal of Computer-Aided Molecular Design
ISSN:
0920-654X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Blind predictions of octanol/water partition coefficients and pKa at 298.15 K for 22 drug-like compounds were made for the SAMPL7 challenge. Octanol/water partition coefficients were predicted from solvation free energies computed using electronic structure calculations with the SM12, SM8 and SMD solvation models. Within these calculations we compared the use of gas- and solution-phase optimized geometries of the solute. Based on these calculations we found that in general the use of solution phase-optimized geometries increases the affinity of the solutes for water as compared to octanol, with the use of gas-phase optimized geometries resulting in the better agreement with experiment. The pKa is computed using the direct approach, scaled solvent-accessible surface model, and the inclusion of an explicit water molecule, where the latter two methods have previously been shown to offer improved predictions as compared to the direct approach. We find that the use of an explicit water molecule provides superior predictions, and that the predicted macroscopic pKa is sensitive to the employed microstates.
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Articulos(CCT - NOA SUR)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - NOA SUR
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - NOA SUR
Citación
Rodríguez, Sergio Antonio; Tran, Jasmine Vy; Sabatino, Spencer J.; Paluch, Andrew S.; Predicting octanol/water partition coefficients and pKa for the SAMPL7 challenge using the SM12, SM8 and SMD solvation models; Springer; Journal of Computer-Aided Molecular Design; 36; 9; 9-2022; 687-705
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