Conjugated Quantitative Structure-Property Relationship Models: Application to Simultaneous Prediction of Tautomeric Equilibrium Constants and Acidity of Molecules.
J Chem Inf Model
; 59(11): 4569-4576, 2019 11 25.
Article
em En
| MEDLINE
| ID: mdl-31638794
ABSTRACT
Here, we describe a concept of conjugated models for several properties (activities) linked by a strict mathematical relationship. This relationship can be directly integrated analytically into the ridge regression (RR) algorithm or accounted for in a special case of "twin" neural networks (NN). Developed approaches were applied to the modeling of the logarithm of the prototropic tautomeric constant (logKT) which can be expressed as the difference between the acidity constants (pKa) of two related tautomers. Both conjugated and individual RR and NN models for logKT and pKa were developed. The modeling set included 639 tautomeric constants and 2371 acidity constants of organic molecules in various solvents. A descriptor vector for each reaction resulted from the concatenation of structural descriptors and some parameters for reaction conditions. For the former, atom-centered substructural fragments describing acid sites in tautomer molecules were used. The latter were automatically identified using the condensed graph of reaction approach. Conjugated models performed similarly to the best individual models for logKT and pKa. At the same time, the physically grounded relationship between logKT and pKa was respected only for conjugated but not individual models.
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1
Bases de dados:
MEDLINE
Assunto principal:
Compostos Orgânicos
/
Preparações Farmacêuticas
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
J Chem Inf Model
Assunto da revista:
INFORMATICA MEDICA
/
QUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Federação Russa