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BioMed Research InternationalVolume 2014 2014, Article ID 257040, 7 pages

Research Article

Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia

Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia

Department of Neurochemistry, Stockholm University, 106 91 Stockholm, Sweden

Received 27 February 2014; Accepted 15 May 2014; Published 24 July 2014

Academic Editor: Maria Jerzykiewicz

Copyright © 2014 Alfonso T. García-Sosa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The binding affinity of a series of cell-penetrating peptides CPP was modeled through docking and making use of the number of intermolecular hydrogen bonds, lipophilic contacts, and the number of sp3 molecular orbital hybridization carbons. The new ranking of the peptides is consistent with the experimentally determined efficiency in the downregulation of luciferase activity, which includes the peptides’ ability to bind and deliver the siRNA into the cell. The predicted structures of the complexes of peptides to siRNA were stable throughout 10 ns long, explicit water molecular dynamics simulations. The stability and binding affinity of peptide-siRNA complexes was related to the sidechains and modifications of the CPPs, with the stearyl and quinoline groups improving affinity and stability. The reranking of the peptides docked to siRNA, together with explicit water molecular dynamics simulations, appears to be well suited to describe and predict the interaction of CPPs with siRNA.

Autor: Alfonso T. García-Sosa, Indrek Tulp, Kent Langel, and Ülo Langel



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