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Improved Modeling of Peptide-Protein Binding Through Global Docking and Accelerated Molecular Dynamics Simulations
dc.contributor.author | Wang, Jinan | |
dc.contributor.author | Alekseenko, Andrey | |
dc.contributor.author | Kozakov, Dima | |
dc.contributor.author | Miao, Yinglong | |
dc.date.accessioned | 2020-06-12T18:19:44Z | |
dc.date.available | 2020-06-12T18:19:44Z | |
dc.date.issued | 2019-10-30 | |
dc.identifier.citation | Wang, J., Alekseenko, A., Kozakov, D., & Miao, Y. (2019). Improved Modeling of Peptide-Protein Binding Through Global Docking and Accelerated Molecular Dynamics Simulations. Frontiers in molecular biosciences, 6, 112. https://doi.org/10.3389/fmolb.2019.00112 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/30456 | |
dc.description | This work is licensed under a Creative Commons Attribution 4.0 International License. | en_US |
dc.description.abstract | Peptides mediate up to 40% of known protein-protein interactions in higher eukaryotes and play a key role in cellular signaling, protein trafficking, immunology, and oncology. However, it is challenging to predict peptide-protein binding with conventional computational modeling approaches, due to slow dynamics and high peptide flexibility. Here, we present a prototype of the approach which combines global peptide docking using ClusPro PeptiDock and all-atom enhanced simulations using Gaussian accelerated molecular dynamics (GaMD). For three distinct model peptides, the lowest backbone root-mean-square deviations (RMSDs) of their bound conformations relative to X-ray structures obtained from PeptiDock were 3.3–4.8 Å, being medium quality predictions according to the Critical Assessment of PRediction of Interactions (CAPRI) criteria. GaMD simulations refined the peptide-protein complex structures with significantly reduced peptide backbone RMSDs of 0.6–2.7 Å, yielding two high quality (sub-angstrom) and one medium quality models. Furthermore, the GaMD simulations identified important low-energy conformational states and revealed the mechanism of peptide binding to the target proteins. Therefore, PeptiDock+GaMD is a promising approach for exploring peptide-protein interactions. | en_US |
dc.publisher | Frontiers Media | en_US |
dc.rights | Copyright © 2019 Wang, Alekseenko, Kozakov and Miao. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Peptide-protein binding | en_US |
dc.subject | Peptide docking | en_US |
dc.subject | PeptiDock | en_US |
dc.subject | Gaussian accelerated molecular dynamics (GaMD) | en_US |
dc.subject | Peptide flexibility | en_US |
dc.title | Improved Modeling of Peptide-Protein Binding Through Global Docking and Accelerated Molecular Dynamics Simulations | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Wang, Jinan | |
kusw.kuauthor | Miao, Yinglong | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.3389/fmolb.2019.00112 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC6835073 | en_US |
dc.rights.accessrights | openAccess | en_US |