Table of Contents
Journal of Biophysics
Volume 2017 (2017), Article ID 1059216, 12 pages
Research Article

Trends in the Binding of Cell Penetrating Peptides to siRNA: A Molecular Docking Study

1Postgraduate Institute of Science, University of Peradeniya, 20400 Peradeniya, Sri Lanka
2Department of Chemistry, University of Peradeniya, 20400 Peradeniya, Sri Lanka

Correspondence should be addressed to R. J. K. U. Ranatunga

Received 28 October 2016; Accepted 15 January 2017; Published 21 February 2017

Academic Editor: Jianwei Shuai

Copyright © 2017 P. V. G. M. Rathnayake 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 use of gene therapeutics, including short interfering RNA (siRNA), is limited by the lack of efficient delivery systems. An appealing approach to deliver gene therapeutics involves noncovalent complexation with cell penetrating peptides (CPPs) which are able to penetrate the cell membranes of mammals. Although a number of CPPs have been discovered, our understanding of their complexation and translocation of siRNA is as yet insufficient. Here, we report on computational studies comparing the binding affinities of CPPs with siRNA, considering a variety of CPPs. Specifically, seventeen CPPs from three different categories, cationic, amphipathic, and hydrophobic CPPs, were studied. Molecular mechanics were used to minimize structures, while molecular docking calculations were used to predict the orientation and favorability of sequentially binding multiple peptides to siRNA. Binding scores from docking calculations were highest for amphipathic peptides over cationic and hydrophobic peptides. Results indicate that initial complexation of peptides will likely occur along the major groove of the siRNA, driven by electrostatic interactions. Subsequent binding of CPPs is likely to occur in the minor groove and later on bind randomly, to siRNA or previously bound CPPs, through hydrophobic interactions. However, hydrophobic CPPs do not show this binding pattern. Ultimately binding yields a positively charged nanoparticle capable of noninvasive cellular import of therapeutic molecules.