Improved Modeling of Peptide-Protein Binding Through Global Docking and Accelerated Molecular Dynamics Simulations
Improved Modeling of Peptide-Protein Binding Through Global Docking and Accelerated Molecular Dynamics Simulations
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DOI：
10.3389/fmolb.2019.00112
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发表时间：
2019-08
影响因子：
5
通讯作者：
Jinan Wang;Andrey Alekseenko;D. Kozakov;Yinglong Miao
中科院分区：
文献类型：
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作者：
Jinan Wang;Andrey Alekseenko;D. Kozakov;Yinglong Miao
肽在较高的真核生物中介导多达40％的已知蛋白质蛋白相互作用，并在细胞信号传导，蛋白质运输，免疫学和肿瘤学中起关键作用。缓慢的动力学和高肽的灵活性。使用高斯加速分子动力学（GAMD）的模拟。根据对相互作用的预测（CAPRI）标准的质量预测。肽骨架RMSD显着降低了0.6Å - 2.7Å，产生了两个高质量（亚角）和一个中等质量模型。因此，蛋白质。
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 Å – 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 Å – 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.