Thumbnail Image
Publication

Improved Modeling of Peptide-Protein Binding Through Global Docking and Accelerated Molecular Dynamics Simulations

Wang, Jinan
; 
Alekseenko, Andrey
; 
Kozakov, Dima
; 
Miao, Yinglong
Citations
Altmetric:
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.
Description
This work is licensed under a Creative Commons Attribution 4.0 International License.
Date
2019-10-30
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers Media
Collections
Molecular Biosciences Scholarly Works
Show all metadata
Files
Thumbnail Image
Wang_2019.pdf
Adobe PDF, 1.84 MB
Research Projects
Organizational Units
Journal Issue
Keywords
Peptide-protein binding, Peptide docking, PeptiDock, Gaussian accelerated molecular dynamics (GaMD), Peptide flexibility
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
URI
https://hdl.handle.net/1808/30456
DOI
10.3389/fmolb.2019.00112
Embedded videos