title: Computational selection of RNA aptamer against angiopoietin-2 and experimental evaluation.
abstract: Angiogenesis plays a decisive role in the growth and spread of cancer and angiopoietin-2 (Ang2) is in the spotlight of studies for its unique role in modulating angiogenesis. The aim of this study was to introduce a computational simulation approach to screen aptamers with high binding ability for Ang2. We carried out computational simulations of aptamer-protein interactions by using ZDOCK and ZRANK functions in Discovery Studio 3.5 starting from the available information of aptamers generated through the systematic evolution of ligands by exponential enrichment (SELEX) in the literature. From the best of three aptamers on the basis of ZRANK scores, 189 sequences with two-point mutations were created and simulated with Ang2. Then, we used a surface plasmon resonance (SPR) biosensor to test 3 mutant sequences of high ZRANK scores along with a high and a low affinity binding sequence as reported in the literature. We found a selected RNA aptamer has a higher binding affinity and SPR response than a reported sequence with the highest affinity. This is the first study of in silico selection of aptamers against Ang2 by using the ZRANK scoring function, which should help to increase the efficiency of selecting aptamers with high target-binding ability.
authors: Department of Biomedical Informatics, Asia University, Taichung City 41354, Taiwan ; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City 40402, Taiwan.
authors: Wen-Pin
authors: WP
authors: Hu
authors: Department of Biomedical Informatics, Asia University, Taichung City 41354, Taiwan.
authors: Jangam Vikram
authors: JV
authors: Kumar
authors: Graduate Institute of Biomedical Engineering, National Central University, Jhongli 32001, Taiwan.
authors: Chun-Jen
authors: CJ
authors: Huang
authors: Department of Chemical and Materials Engineering, National Central University, Jhongli 32001, Taiwan.
authors: Wen-Yih
authors: WY
authors: Chen
mesh_terms: D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D052156:SELEX Aptamer Technique; D020349:Surface Plasmon Resonance
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D052157:Aptamers, Nucleotide