PatchDock and SymmDock: servers for rigid and symmetric docking

Stroopinsky, Dina; Inbar, Yuval; Nussinov, Ruth; Wolfson, Haim J.

doi:10.1093/nar/gki481

Cited by 2,675 publications

(1,870 citation statements)

References 28 publications

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“…The docking was also performed with PatchDock [14,32] in order to increase the accuracy of docking. PatchDock is geometry-based molecular docking tool.…”

Section: Receptor-ligand Interactionsmentioning

confidence: 99%

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

et al. 2017

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Chikungunya fever is an arboviral infection caused by the Chikungunya virus (CHIKV) and is transmitted by Aedes mosquito. The envelope protein (E2) of Chikungunya virus is involved in attachment of virion with the host cell. The present study was conceptualized to determine the structure of E2 protein of CHIKV and to identify the potential viral entry inhibitors. The secondary and tertiary structure of E2 protein was determined using bioinformatics tools. The mutational analysis of the E2 protein suggested that mutations may stabilize or de-stabilize the structure which may affect the structure-function relationship. In silico screening of various compounds from different databases identified two lead molecules i.e. phenothiazine and bafilomycin. Molecular docking and MD simulation studies of the E2 protein and compound complexes was carried out. This analysis revealed that bafilomycin has high docking score and thus high binding affinity with E2 protein suggesting stable protein-ligand interaction. Further, MD simulations suggested that both the compounds were stabilizing E2 protein. Thus, bafilomycin and phenothiazine may be considered as the lead compounds in terms of potential entry inhibitor for CHIKV. Further, these results should be confirmed by comprehensive cell culture, cytotoxic assays and animal experiments. Certain derivatives of phenothiazines can also be explored in future studies for entry inhibitors against CHIKV. The present investigation thus provides insight into protein structural dynamics of the envelope protein of CHIKV. In addition the study also provides information on the dynamics of interaction of E2 protein with entry inhibitors that will contribute towards structure based drug design.

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“…The docking was also performed with PatchDock [14,32] in order to increase the accuracy of docking. PatchDock is geometry-based molecular docking tool.…”

Section: Receptor-ligand Interactionsmentioning

confidence: 99%

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

et al. 2017

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“…[53,54] The top 3 structures with the highest negative global energy score were taken for analysis and hydrogen bond distances were measured using the UCSF Chimera software. [55] The structures of GA, ECG, and EGCG were drawn in GaussView 5.0.8 [56] and subsequently optimized in Gaussian 09 [57] using B3LYP [58] method and 6-31G basis set.…”

Section: Docking Studiesmentioning

confidence: 99%

β‐cyclodextrin encapsulated polyphenols as effective antioxidants

et al. 2017

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Formation of dityrosine (DT) cross-linkages in proteins is one of the most widely used markers of oxidative stress. Ribonuclease A (RNase A) has 6 Tyr residues and shows a characteristic DT fluorescence peak upon oxidation in addition to major changes in its secondary structure. DT formation can be prevented by using polyphenols (GA, ECG, and EGCG) which are known to have strong antioxidant activity. However, it has been observed that ECG and EGCG initiate protein oligomerization due to protein-polyphenol cross-linkages. To prevent the formation of such crosslinkages we have used b-cyclodextrin (b-CD) to encapsulate the polyphenols and studied its antioxidant properties along with that of free polyphenols. The polyphenol/b-cyclodextrin (b-CD) inclusion complexes not only prevent DT formation but also reduce protein oligomerization. This may be attributed to the fact that the quinone forming rings of ECG and EGCG become encapsulated in the cavity of b-CD and are no longer available for protein cross-linking.b-cyclodextrin encapsulation, dityrosine, oxidative stress, polyphenols, protein oligomerization | I N TR ODU C TI ONBiological aging in mammalian cells is a direct indication of oxidative stress in proteins. [1] These oxidatively modified forms of proteins are generated due to the presence of reactive oxygen species (ROS) such as hydroxyl and superoxide free radicals. [2,3] Persulfates, a key ingredient in flour, are a source of sulfate (SO 2 4 ) free radicals under neutral pH. [4,5] Due to the higher oxidizing power of the sulfate radical (E 0 5 12.60 V) and longer half-life period over the OH radical, it has drawn attention in recent times as a powerful oxidizing agent. [6][7][8] Many chemical and cosmetic industries require persulfates as their key components [9] and workers often suffer from skin and respiratory diseases due to hypersensitive reactions. [10] Generally, the lower thermal energy at room temperature (25-508C) is not sufficient enough to activate persulfate, but generation of SO 2 4 radical is facilitated in presence of metal cations. Since proteins tend to lose their structure and function at high temperatures, [11] we have carried out the oxidation of ribonuclease A (RNase A) in presence of persulfate using cobalt (II) ion at 378C. [12] Cobalt is an integral component of vitamin B12 and thus physiologically found in most tissues mainly in liver and kidney. [13,14] Gill et al., reported the formation of oligomeric species (dimer, trimer, tetramer) when RNase A was exposed to KHSO 5 in presence of metal ions such as Ni 21 and Cu 21 and the high molecular weight species were identified using SDS-PAGE. [12] An important biomarker of oxidative stress is the dityrosine moiety generated due to the covalent linkage of two Tyr residues. [15] Dityrosine bond formation is an indication of aging, and disease related problems since it generally occurs during amyloid fibril formation, [16] Parkinson disease, [17] cerebrospinal fluid damage, [18] and also in the cataract of the eye lens. [19,20] D...

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“…The protein-protein docking of the UBE2D4 with its natural substrate ubiquitin ligase CHIP is carried out using PatchDock server [48] to identify the binding site region and residues in the UBE2D4 protein.…”

Section: Active Site Predictionmentioning

confidence: 99%

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery–a structure-based approach

et al. 2016

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Cancer progression is a global burden. The incidence and mortality now reach 30 million deaths per year. Several pathways of cancer are under investigation for the discovery of effective therapeutics. The present study highlights the structural details of the ubiquitin protein 'Ubiquitin-conjugating enzyme E2D4' (UBE2D4) for the novel lead structure identification in cancer drug discovery process. The evaluation of 3D structure of UBE2D4 was carried out using homology modelling techniques. The optimized structure was validated by standard computational protocols. The active site region of the UBE2D4 was identified using computational tools like CASTp, Q-site Finder and SiteMap. The hydrophobic pocket which is responsible for binding with its natural receptor ubiquitin ligase CHIP (C-terminal of Hsp 70 interacting protein) was identified through proteinprotein docking study. Corroborating the results obtained from active site prediction tools and protein-protein docking study, the domain of UBE2D4 which is responsible for cancer cell progression is sorted out for further docking study. Virtual screening with large structural database like CB_Div Set and Asinex BioDesign small molecular structural database was carried out. The obtained new ligand molecules that have shown affinity towards UBE2D4 were considered for ADME prediction studies. The identified new ligand molecules with acceptable parameters of docking, ADME are considered as potent UBE2D4 enzyme inhibitors for cancer therapy.

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PatchDock and SymmDock: servers for rigid and symmetric docking

Cited by 2,675 publications

References 28 publications

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

β‐cyclodextrin encapsulated polyphenols as effective antioxidants

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery–a structure-based approach

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