Using Membrane Partitioning Simulations To Predict Permeability of Forty-Nine Drug-Like Molecules.
J Chem Inf Model
; 59(1): 236-244, 2019 01 28.
Article
en En
| MEDLINE
| ID: mdl-30540467
ABSTRACT
A simple descriptor calculated from molecular dynamics simulations of the membrane partitioning event is found to correlate well with experimental measurements of passive membrane permeation from the high-throughput MDCK-LE assay using a data set of 49 drug-like molecules. This descriptor approximates the energy cost of translocation across the hydrophobic membrane core (flip-flop), which for many molecules limits permeability. Performance is found to be superior in comparison to calculated properties such as clogP, clogD, or polar surface area. Furthermore, the atomistic simulations provide a structural understanding of the partitioned drug-membrane complex, facilitating medicinal chemistry optimization of membrane permeability.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Permeabilidad de la Membrana Celular
/
Simulación de Dinámica Molecular
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Chem Inf Model
Asunto de la revista:
INFORMATICA MEDICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos