Exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method

Abstract The stochastic tunnelling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method was applied to the search for the most stable biomolecular complexes in water by using the MARTINI coarse-grained (CG) model. The epithelial cell adhesion molecule (EpCAM, PDB code: 4MZV) was used as an...

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Autores principales: Chia-Hao Su, Hui-Lung Chen, Shin-Pon Ju, Tai-Ding You, Yu-Sheng Lin, Ta-Feng Tseng
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:19ac1139dfff4ed09241b21be840272d2021-12-02T18:25:03ZExploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method10.1038/s41598-021-90907-y2045-2322https://doaj.org/article/19ac1139dfff4ed09241b21be840272d2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90907-yhttps://doaj.org/toc/2045-2322Abstract The stochastic tunnelling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method was applied to the search for the most stable biomolecular complexes in water by using the MARTINI coarse-grained (CG) model. The epithelial cell adhesion molecule (EpCAM, PDB code: 4MZV) was used as an EpCAM adaptor for an EpA (AptEpA) benchmark target molecule. The effects of two adsorption positions on the EpCAM were analysed, and it is found that the AptEpA adsorption configuration located within the EpCAM pocket-like structure is more stable and the energy barrier is lower due to the interaction with water. By the root mean square deviation (RMSD), the configuration of EpCAM in water is more conservative when the AptEpA binds to EpCAM by attaching to the pocket space of the EpCAM dimer. For AptEpA, the root mean square fluctuation (RMSF) analysis result indicates Nucleobase 1 and Nucleobase 2 display higher flexibility during the CGMD simulation. Finally, from the binding energy contour maps and histogram plots of EpCAM and each AptEpA nucleobase, it is clear that the binding energy adsorbed to the pocket-like structure is more continuous than that energy not adsorbed to the pocket-like structure. This study has proposed a new numerical process for applying the STUN-BH-DMD with the CG model, which can reduce computational details and directly find a more stable AptEpA/EpCAM complex in water.Chia-Hao SuHui-Lung ChenShin-Pon JuTai-Ding YouYu-Sheng LinTa-Feng TsengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Chia-Hao Su
Hui-Lung Chen
Shin-Pon Ju
Tai-Ding You
Yu-Sheng Lin
Ta-Feng Tseng
Exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method
description Abstract The stochastic tunnelling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method was applied to the search for the most stable biomolecular complexes in water by using the MARTINI coarse-grained (CG) model. The epithelial cell adhesion molecule (EpCAM, PDB code: 4MZV) was used as an EpCAM adaptor for an EpA (AptEpA) benchmark target molecule. The effects of two adsorption positions on the EpCAM were analysed, and it is found that the AptEpA adsorption configuration located within the EpCAM pocket-like structure is more stable and the energy barrier is lower due to the interaction with water. By the root mean square deviation (RMSD), the configuration of EpCAM in water is more conservative when the AptEpA binds to EpCAM by attaching to the pocket space of the EpCAM dimer. For AptEpA, the root mean square fluctuation (RMSF) analysis result indicates Nucleobase 1 and Nucleobase 2 display higher flexibility during the CGMD simulation. Finally, from the binding energy contour maps and histogram plots of EpCAM and each AptEpA nucleobase, it is clear that the binding energy adsorbed to the pocket-like structure is more continuous than that energy not adsorbed to the pocket-like structure. This study has proposed a new numerical process for applying the STUN-BH-DMD with the CG model, which can reduce computational details and directly find a more stable AptEpA/EpCAM complex in water.
format article
author Chia-Hao Su
Hui-Lung Chen
Shin-Pon Ju
Tai-Ding You
Yu-Sheng Lin
Ta-Feng Tseng
author_facet Chia-Hao Su
Hui-Lung Chen
Shin-Pon Ju
Tai-Ding You
Yu-Sheng Lin
Ta-Feng Tseng
author_sort Chia-Hao Su
title Exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method
title_short Exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method
title_full Exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method
title_fullStr Exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method
title_full_unstemmed Exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method
title_sort exploring the most stable aptamer/target molecule complex by the stochastic tunnelling-basin hopping-discrete molecular dynamics method
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/19ac1139dfff4ed09241b21be840272d
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