The HDOCK server for integrated protein–protein docking

Yan, Yumeng; Tao, Huanyu; He, Jiahua; Huang, Sheng‐You

doi:10.1038/s41596-020-0312-x

Cited by 975 publications

(739 citation statements)

References 107 publications

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“…The complex structure between the SARS-CoV-2 RBD protein and the human ACE2 molecule was predicted using our hybrid protein-protein docking algorithm, HDOCK [40][41][42][43]. Specifically, given the individual structures of the SARS-CoV-2 RBD protein and the human ACE2 molecule, HDOCK globally samples all possible binding modes between the two proteins through a fast Fourier transform (FFT)-based search strategy [42].…”

Section: Protein-protein Dockingmentioning

confidence: 99%

Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2

Tao

Yan

et al. 2020

Viruses

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162

190

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The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2.Viruses 2020, 12, 428 2 of 11 origin and is 96% identical at the whole-genome level to a bat SARS-like coronavirus [22]. In addition, SARS-CoV-2 is also closely related to other SARS-like coronaviruses and shares a 79.5% sequence identity to SARS-CoV [22]. For some encoded proteins like coronavirus main proteinase (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), the sequence identity is even higher and can be as high as 96% between SARS-CoV-2 and SARS-CoV [23]. Therefore, it was thought that SARS-CoV-2 would function in a similar way to SARS-CoV in the human-infection and pathogenic mechanism [22][23][24].Coronaviruses use the surface spike (S) glycoprotein on the coronavirus envelope to attach host cells and mediate host cell membrane and viral membrane fusion during infection [25]. The spike protein includes two regions, S1 and S2, where S1 is for host cell receptor binding and S2 is for membrane fusion. The S1 region also includes an N-terminal domain (NTD) and three C-terminal domains (CTD1, CTD2, and CTD3) [26]. For SARS-CoV, the receptor binding domain (RBD) is located in the CTD1 of the S1 region. SARS-CoV attaches the human host cells through the binding of the RBD protein to the angiotensin-converting enzyme II (ACE2) [27,28]. Therefore, the interaction between RBD and ACE2 is a prerequisite for the human infection with SARS-CoV. Given the high homology between SARS-CoV and SARS-CoV-2, it was expected that SARS-CoV-2 would also use the ACE2 molecule as the receptor to enter human cells [24,29]. This hypothesis was further experimentally confirmed by the virus infectivity studies from the Shi group, in which SARS-CoV-2 is able to use the ACE2 proteins from humans, Chinese horseshoe bats, and civ...

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Section: Protein-protein Dockingmentioning

confidence: 99%

Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2

Tao

Yan

et al. 2020

Viruses

Self Cite

162

190

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“…The complex structure between the 2019-nCoV RBD protein and the human ACE2 molecule was predicted using our hybrid protein-protein docking algorithm, HDOCK [27][28][29][30]. Specifically, given the individual structures of the spike RBD protein and the human ACE2 molecule, HDOCK will globally sample all possible binding modes between the two proteins through a fast Fourier transform (FFT) search strategy [30].…”

Section: Protein-protein Dockingmentioning

confidence: 99%

Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)

Tao

Yan

et al. 2020

Preprint

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AbstractSince December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

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“…Docking analyses were performed with the L. albus γC model and β-mannosidase with the best resolution in the PDB repository, namely, the enzyme from T. harzianum ThMan2A (PDB: 4CVU) [ 55 ]. These elaborations were performed with different on-line available software: pyDockWEB [ 64 ], ClusPro 2.0 [ 65 ], PRISM 2.0 [ 66 , 67 ], GRAMM-X Protein-Protein Docking Web Server v.1.2.0 [ 68 ], HDOCK Server [ 69 ] and FRODOCK [ 70 ]. All the tools used compute protein–protein interaction using Fast Fourier Transform and rigid-body structural matching, followed by the refinement of the predicted complexes and global energy calculation.…”

Section: Methodsmentioning

confidence: 99%

Lupinus albus γ-Conglutin, a Protein Structurally Related to GH12 Xyloglucan-Specific Endo-Glucanase Inhibitor Proteins (XEGIPs), Shows Inhibitory Activity against GH2 β-Mannosidase

Benedetti

Galanti

Capraro

et al. 2020

IJMS

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γ-conglutin (γC) is a major protein of Lupinus albus seeds, but its function is still unknown. It shares high structural similarity with xyloglucan-specific endo-glucanase inhibitor proteins (XEGIPs) and, to a lesser extent, with Triticum aestivum endoxylanase inhibitors (TAXI-I), active against fungal glycoside hydrolases GH12 and GH11, respectively. However, γC lacks both these inhibitory activities. Since β-galactomannans are major components of the cell walls of endosperm in several legume plants, we tested the inhibitory activity of γC against a GH2 β-mannosidase (EC 3.2.1.25). γC was actually able to inhibit the enzyme, and this effect was enhanced by the presence of zinc ions. The stoichiometry of the γC/enzyme interaction was 1:1, and the calculated Ki was 1.55 μM. To obtain further insights into the interaction between γC and β-mannosidase, an in silico structural bioinformatic approach was followed, including some docking analyses. By and large, this work describes experimental findings that highlight new scenarios for understanding the natural role of γC. Although structural predictions can leave space for speculative interpretations, the full complexity of the data reported in this work allows one to hypothesize mechanisms of action for the basis of inhibition. At least two mechanisms seem plausible, both involving lupin-γC-peculiar structures.

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The HDOCK server for integrated protein–protein docking

Cited by 975 publications

References 107 publications

Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2

Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2

Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)

Lupinus albus γ-Conglutin, a Protein Structurally Related to GH12 Xyloglucan-Specific Endo-Glucanase Inhibitor Proteins (XEGIPs), Shows Inhibitory Activity against GH2 β-Mannosidase

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