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
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- 作者：Fabi谩n Avila-Salas ; Claudia Sandoval ; Julio Caballero ; Sergio Gui帽ez-Molinos ; Leonardo S. Santos ; Ra煤l E. Cachau ; Fernando D. Gonz谩lez-Nilo
- 刊名：The Journal of Physical Chemistry B
- 出版年：2012
- 出版时间：February 23, 2012
- 年：2012
- 卷：116
- 期：7
- 页码：2031-2039
- 全文大小：526K
- 年卷期：v.116,no.7(February 23, 2012)
- ISSN：1520-5207
文摘
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鈥揹rug complexes, which can be used for in silico prediction of dendrimer鈥揹rug affinity. Initially, a large-scale sampling of different dendrimer鈥揹rug 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鈥揋4 dendrimer. The affinities were also characterized experimentally by using Cooks鈥?kinetic method to calculate PAMAM鈥揹rug dissociation constants. The quantitative structure鈥揳ctivity relationship between the interaction energies and dissociation constants showed statistical correlations with r2 > 0.9.