title: Structure-based design of peptides against G3BP with cytotoxicity on tumor cells.
abstract: Herein, we report a successful application of molecular modeling techniques to design two novel peptides with cytotoxicity on tumor cells. First, the interactions between the nuclear transport factor 2 (NTF2)-like domain of G3BP and the SH3 domain of RasGAP were studied by a well-designed protocol, which combines homology modeling, protein/protein docking, molecular dynamics simulations, molecular mechanics/generalized born surface area (MM/GBSA) free energy calculations, and MM/GBSA free energy decomposition analysis together. Then, based on the theoretical predictions, two novel peptides were designed and synthesized for biological assays, and they showed an obvious sensitizing effect on cis-platin. Furthermore, the designed peptides had no significant effects on normal cells, while cis-platin did. Our results demonstrate that it is feasible to use the peptides to enhance the efficacy of clinical drugs and to kill cancer cells selectively. We believe that our work should be very useful for finding new therapies for cancers.
authors.affiliation: Department of Chemistry, Graduate University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wei
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Yuanhua
authors.initials: Y
authors.lastname: Cheng
authors.forename: Lingling
authors.initials: L
authors.lastname: Geng
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.forename: Tingjun
authors.initials: T
authors.lastname: Hou
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Ji
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology*; D004265:DNA Helicases; D006367:HeLa Cells; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D013816:Thermodynamics; D018909:src Homology Domains / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D003603:Cytotoxins; D010455:Peptides; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases