title: Peptide-ligand binding modeling of siRNA with cell-penetrating peptides.
abstract: 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.
authors.affiliation: Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia.
authors.forename: Alfonso T
authors.initials: AT
authors.lastname: García-Sosa
authors.affiliation: Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia.
authors.forename: Indrek
authors.identifier: 0000-0001-6967-5530
authors.initials: I
authors.lastname: Tulp
authors.affiliation: Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
authors.forename: Kent
authors.identifier: 0000-0001-8446-6286
authors.initials: K
authors.lastname: Langel
authors.affiliation: Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia ; Department of Neurochemistry, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Ülo
authors.initials: Ü
authors.lastname: Langel
mesh_terms: D000595:Amino Acid Sequence; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D008024:Ligands; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011804:Quinolines / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D008024:Ligands; D010455:Peptides; D011804:Quinolines; D034741:RNA, Small Interfering; D014867:Water; C037219:quinoline