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Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation
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 A...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383501/ https://www.ncbi.nlm.nih.gov/pubmed/25866800 http://dx.doi.org/10.1155/2015/658712 |
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author | Hu, Wen-Pin Kumar, Jangam Vikram Huang, Chun-Jen Chen, Wen-Yih |
author_facet | Hu, Wen-Pin Kumar, Jangam Vikram Huang, Chun-Jen Chen, Wen-Yih |
author_sort | Hu, Wen-Pin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4383501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-43835012015-04-12 Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation Hu, Wen-Pin Kumar, Jangam Vikram Huang, Chun-Jen Chen, Wen-Yih Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2015 2015-03-19 /pmc/articles/PMC4383501/ /pubmed/25866800 http://dx.doi.org/10.1155/2015/658712 Text en Copyright © 2015 Wen-Pin Hu et al. https://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Article Hu, Wen-Pin Kumar, Jangam Vikram Huang, Chun-Jen Chen, Wen-Yih Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation |
title | Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation |
title_full | Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation |
title_fullStr | Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation |
title_full_unstemmed | Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation |
title_short | Computational Selection of RNA Aptamer against Angiopoietin-2 and Experimental Evaluation |
title_sort | computational selection of rna aptamer against angiopoietin-2 and experimental evaluation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383501/ https://www.ncbi.nlm.nih.gov/pubmed/25866800 http://dx.doi.org/10.1155/2015/658712 |
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