Atomic-level characterization and cilostazol affinity of poly(lactic acid) nanoparticles conjugated with differentially charged hydrophilic molecules

Indexación: Scopus.M.F.M. acknowledges support from CONICYT-PFCHA/Doctorado Nacional/2014-21140225. M.M.M. thanks the FONCyT PICT-2015-2191, CONICET PIP 11220110100992, Secyt, Universidad Nacional de Cordoba. C.V. acknowledges support from CONICYT under FONDECYT #1161438 and BASAL Grant FB0807, MECESUP PMI-UAB1301, and H2020-MSCA-RISE-2016 #734801 MAGNAMED. The authors thank the High-Performance Computational Center (CCAD UNC) and Escuela de Ingeniería Civil en Bioinformática (Universidad de Talca) for access to supercomputers.Nanotherapeutics is a promising field for numerous diseases and represents the forefront of modern medicine. In the present work, full atomistic computer simulations were applied to study poly(lactic acid) (PLA) nanoparticles conjugated with polyethylene glycol (PEG). The formation of this complex system was simulated using the reactive polarizable force field (ReaxFF). A full picture of the morphology, charge and functional group distribution is given. We found that all terminal groups (carboxylic acid, methoxy and amino) are randomly distributed at the surface of the nanoparticles. The surface design of NPs requires that the charged groups must surround the surface region for an optimal functionalization/charge distribution, which is a key factor in determining physicochemical interactions with different biological molecules inside the organism. Another important point that was investigated was the encapsulation of drugs in these nanocarriers and the prediction of the polymer-drug interactions, which provided a better insight into structural features that could affect the effectiveness of drug loading. We employed blind docking to predict NP-drug affinity testing on an antiaggregant compound, cilostazol. The results suggest that the combination of molecular dynam ics ReaxFF simulations and blind docking techniques can be used as an explorative tool prior to experiments, which is useful for rational design of new drug delivery systems. © 2018 Matus et al.https://www.beilstein-journals.org/bjnano/articles/9/12

The behavior of single-molecule junctions predicted by atomistic simulations

Molecular dynamic simulations in combination with energy minimizations are used in order to understand the basis of the novel experiments reported recently by Haiss et al. (W. Haiss, C. Wang, I. Grace, A.S. Batsanov, D.J. Schiffrin, S.J. Higgins, M.R. Bryce, C.J. Lambert, R.J. Nichols, Nature Mater. 5 (2006) 995). Our model suggests that single-molecule junctions produced by the trapping method can be reached when the STM tip – substrate surface separation is smaller than 8 Å. Additionally, our model predicts that the effect of the electric field on the attachment/detachment process can be neglected. Keywords: Single-molecule junctions, Computer simulations, Trapping metho