HawkDock: a web server to predict and analyze the protein–protein complex based on computational docking and MM/GBSA

Weng, Gaoqi; Wang, Ercheng; Wang, Zhe; Liu, Hui; Zhu, Feng; Li, Dan; Hou, Tingjun

doi:10.1093/nar/gkz397

Cited by 409 publications

(295 citation statements)

References 49 publications

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“…In recent years, development of small molecule modulators targeting protein-protein interactions (PPIs) has emerged as a promising therapeutic intervention in complex diseases (Nero et al, 2014;Nim et al, 2016;Weng et al, 2019). In selecting biologically relevant protein-protein interfaces, the availability of computer-aided drug design (CADD) approach has led to the discovery of small molecules either stabilizing or disrupting the biological processes (Arkin et al, 2014;Laraia et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Molecular Simulation of Oncostatin M and Receptor (OSM–OSMR) Interaction as a Potential Therapeutic Target for Inflammatory Bowel Disease

Yan

Xue

2020

Front. Mol. Biosci.

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Therapeutics targeting cytokines such as the oncostatin M (OSM)-mediated inflammation represent a potential strategy for the treatment of inflammatory bowel disease (IBD). Despite the investigation of the specific role of the interactions between OSM and the receptor (OSMR) in IBD pathogenesis, the 3D structure of the OSM-OSMR complex remains elusive. In this work, the interaction mode between OSM and OSMR at atomic level was predicted by computational simulation approach. The interaction domain of the OSMR was built with the homology modeling method. The near-native structure of the OSM-OSMR complex was obtained by docking, and long-time scale molecular dynamics (MD) simulation in an explicit solvent was further performed to sample the conformations when OSM binds to the OSMR. After getting the equilibrated states of the simulation system, per-residue energy contribution was calculated to characterize the important residues for the OSM-OSMR complex formation. Based on these important residues, eight residues (OSM: Arg100, Leu103, Phe160, and Gln161; OSMR: Tyr214, Ser223, Asp262, and Trp267) were identified as the "hot spots" through computational alanine mutagenesis analysis and verified by additional MD simulation of R100A (one of the identified "hotspots") mutant. Moreover, six cavities were detected at the OSM-OSMR interface through the FTMap analysis, and they were suggested as important binding sites. The predicted 3D structure of the OSM-OSMR complex and the identified "hot spots" constituting the core of the binding interface provide helpful information in understanding the OSM-OSMR interactions, and the detected sites serve as promising targets in designing small molecules to block the interactions.

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Section: Introductionmentioning

confidence: 99%

Molecular Simulation of Oncostatin M and Receptor (OSM–OSMR) Interaction as a Potential Therapeutic Target for Inflammatory Bowel Disease

Yan

Xue

2020

Front. Mol. Biosci.

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“…76 To calculate the binding energy we used the PRODIGY server [27]. 77 The Calculation of contribution of each amino acid in a protein partner 78 was computed with MM-GBSA method implemented in the HawkDock 79 server [23]. Different 3D structures of hACE2, each comprising one of 80 identified variants, were modeled using the BuildModel module of FoldX5 [3].…”

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confidence: 99%

Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

Othman

Bouslama

Brandenburg

et al. 2020

Preprint

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AbstractThe spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.

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“…(MM-GBSA) study was also carried out using HawkDock server. According to the server, the lower score and lower energy corresponds to better scores [61,62,63,64]. The HawkDock server generates several models of docked complex and ranks them by assigning HawkDock scores in the ascending order.…”

Section: Vaccine Protein Disulfide Engineeringmentioning

confidence: 99%

Designing Novel Subunit Vaccines against Herpes Simplex Virus-1 using Reverse Vaccinology Approach

Sarkar

Ullah

2020

Preprint

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Herpes Simplex Virus (HSV) is an infectious virus that is responsible for various types of orofacial and genital infections. Two types of HSV viruses, HSV-1 and HSV-2, are the most dangerous HSV viruses. Every year, millions of people get infected with this menacing virus, however, no satisfactory treatment or vaccine has not yet been discovered to fight against HSV. Although there are some anti-viral therapies, however, studies have showed that such anti-viral therapies may also fail to provide good impact. In this study, a possible subunit vaccine against HSV-1, strain-17, was designed using the tools and reverse vaccinology and bioinformatics. Three potential antigenic envelope glycoproteins were selected from nine envelope glycoproteins, for possible vaccine construction. Potential epitopes capable of inducing high immunogenic response and at the same time have non-allergenicity and conservancy across other strains and species, were selected by some robust analysis, for vaccine construction. Finally, three possible vaccines were designed.Each of the vaccine construct differ from each other only in their adjuvant sequences and based on molecular docking analysis, one best vaccine construct was selected for molecular dynamics simulation study and in silico codon adaptation. The experiment showed that the selected best vaccine should be good candidate against HPV-1, strain-17. However, wet lab study should be conducted on the suggested vaccine(s) for confirming their potentiality, safety and efficacy.

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HawkDock: a web server to predict and analyze the protein–protein complex based on computational docking and MM/GBSA

Cited by 409 publications

References 49 publications

Molecular Simulation of Oncostatin M and Receptor (OSM–OSMR) Interaction as a Potential Therapeutic Target for Inflammatory Bowel Disease

Molecular Simulation of Oncostatin M and Receptor (OSM–OSMR) Interaction as a Potential Therapeutic Target for Inflammatory Bowel Disease

Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

Designing Novel Subunit Vaccines against Herpes Simplex Virus-1 using Reverse Vaccinology Approach

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