Study of Interaction Energies between PAMAM Dendrimer and non-Steroidal Anti-Inflammatory Drug Using a Distributed Computational Strategy and Experimental Analysis by ESI-MS/MS

• Published in: The journal of physical chemistry. B 2012-02, Vol.116 (7), p.2031-2039
• Main Authors: Avila-Salas, Fabián, Sandoval, Claudia, Caballero, Julio, Guiñez-Molinos, Sergio, Santos, Leonardo S., Cachau, Raúl E., González-Nilo, Fernando D.
• Format: Article
• Language: English
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp2069122

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 were generated using Euler angles. Then, each conformation was distributed on different nodes of a GRID computational system; where its interaction energy was calculate by semi-empirical quantum mechanical methods. These energy calculations were performed for four different non-steroidal anti-inflammatory drugs, each showing different affinities for 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 r 2 > 0.9.