Study of interaction energies between the PAMAM dendrimer and nonsteroidal anti-inflammatory drug using a distributed computational strategy and experimental analysis by ESI-MS/MS

Fabián Avila-Salas, Claudia Sandoval, Julio Caballero, Sergio Guiñez-Molinos, Leonardo S. Santos, Raúl E. Cachau, Fernando D. González-Nilo

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

57 Citas (Scopus)

Resumen

The structure of a dendrimer exhibits a large number of internal and superficial cavities, which can be exploited, to capture and deliver small organic molecules, enabling their use in drug delivery. Structure-based modeling and quantum mechanical studies can be used to accurately understand the interactions between functionalized dendrimers and molecules of pharmaceutical and industrial interest. In this study, we implemented a Metropolis Monte Carlo algorithm to calculate the interaction energy of dendrimer-drug complexes, which can be used for in silico prediction of dendrimer-drug affinity. Initially, a large-scale sampling of different dendrimer-drug conformations was generated using Euler angles. Then, each conformation was distributed on different nodes of a GRID computational system, where its interaction energy was calculated by semiempirical quantum mechanical methods. These energy calculations were performed for four different nonsteroidal anti-inflammatory drugs, each showing different affinities for the PAMAM-G4 dendrimer. The affinities were also characterized experimentally by using Cooks' kinetic method to calculate PAMAM-drug dissociation constants. The quantitative structure-activity relationship between the interaction energies and dissociation constants showed statistical correlations with r2 > 0.9.

Idioma originalInglés
Páginas (desde-hasta)2031-2039
Número de páginas9
PublicaciónJournal of Physical Chemistry B
Volumen116
N.º7
DOI
EstadoPublicada - 23 feb 2012

Áreas temáticas de ASJC Scopus

  • Química física y teórica
  • Superficies, recubrimientos y láminas
  • Química de los materiales

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