CovPDB: a high-resolution coverage of the covalent protein–ligand interactome

Gao, Mingjie; Moumbock, Aurélien F. A.; Qaseem, Ammar; Xu, Qianqing; Günther, Stefan

doi:10.1093/nar/gkab868

Cited by 26 publications

(34 citation statements)

References 38 publications

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“…Phytochemicals with published experimental evidence of acting as covalent inhibitors were identified and compiled from CovalentInDB (http://cadd.zju.edu.cn/cidb/) 69 and CovPDB (http://drug-discovery.vm.unifreiburg.de:8000/covpdb/) 70 via a comparison of the chemical structures followed by manual verification.…”

Section: Methodsmentioning

confidence: 99%

IMPPAT 2.0: an enhanced and expanded phytochemical atlas of Indian medicinal plants

Vivek-Ananth

Mohanraj²,

Sahoo

et al. 2022

Preprint

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Compilation, curation, digitization and exploration of the phytochemical space of Indian medicinal plants can expedite ongoing efforts toward natural product and traditional knowledge based drug discovery. To this end, we present IMPPAT 2.0, an enhanced and expanded database, compiling manually curated information on 4010 Indian medicinal plants, 17967 phytochemicals, 1095 therapeutic uses and 1133 traditional Indian medicinal formulations. Notably, IMPPAT 2.0 compiles associations at the level of plant parts, and provides a FAIR compliant non-redundant in silico stereo-aware library of 17967 phytochemicals from Indian medicinal plants. The phytochemical library has been annotated with several useful properties to enable easier exploration of the chemical space. We also filtered a subset of 1335 drug-like phytochemicals of which majority have no similarity to existing approved drugs. Using cheminformatics, we have characterized the molecular complexity and molecular scaffold based structural diversity of the phytochemical space of Indian medicinal plants, and performed a comparative analysis with other chemical libraries. Altogether, IMPPAT is the largest phytochemical atlas of Indian medicinal plants which is accessible at: https://cb.imsc.res.in/imppat/.

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Section: Methodsmentioning

confidence: 99%

IMPPAT 2.0: an enhanced and expanded phytochemical atlas of Indian medicinal plants

Vivek-Ananth

Mohanraj²,

Sahoo

et al. 2022

Preprint

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“…Covalent inhibitors are generally composed of electrophiles that react with nucleophilic residues in enzymes. To date, compounds with a range of electrophilic warheads have been found as covalent inhibitors, including halomethyl carbonyl, vinyl sulfonyl, phosphonate, aldehyde, ketone, vinyl carbonyl, boronic acid, and many more (Table 2 ) [ 30 ]. A novel class of inhibitors dubbed "sulfur tethers" has also garnered interest due to its potential to covalently conjugate cysteines in enzymes [ 31 ].…”

Section: Covalent Inhibition In Biomolecular Systemmentioning

confidence: 99%

“…However, these effects are frequently caused by highly reactive metabolites, and with a better knowledge of the reactivity requirements for covalent inhibitors, interest in the topic has resurged [ 1 ]. Indeed, the recent establishment of the covalent database (COVPDB) from the protein data bank (PDB) has been hailed as a paradigm shift in the covalent drug development paradigm [ 30 ]. Unlike prior covalent databases, which lacked covalent complexes, the CovPDB has a large number of high-resolution co-crystal structures of biologically relevant covalent inhibitors attached to their protein targets.…”

Section: Targeted Covalent Inhibitors and “Warhead” Reactivitymentioning

confidence: 99%

“…Unlike prior covalent databases, which lacked covalent complexes, the CovPDB has a large number of high-resolution co-crystal structures of biologically relevant covalent inhibitors attached to their protein targets. For the curated protein–ligand complexes, Gao and his colleagues manually annotated the covalent inhibitors' chemical structures, defined their pre-reactive electrophilic warhead groups, and covalent-binding mechanisms with their targets [ 30 ].…”

Section: Targeted Covalent Inhibitors and “Warhead” Reactivitymentioning

confidence: 99%

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Docking covalent targets for drug discovery: stimulating the computer-aided drug design community of possible pitfalls and erroneous practices

et al. 2022

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The continuous approval of covalent drugs in recent years for the treatment of diseases has led to an increased search for covalent agents by medicinal chemists and computational scientists worldwide. In the computational parlance, molecular docking which is a popular tool to investigate the interaction of a ligand and a protein target, does not account for the formation of covalent bond, and the increasing application of these conventional programs to covalent targets in early drug discovery practice is a matter of utmost concern. Thus, in this comprehensive review, we sought to educate the docking community about the realization of covalent docking and the existence of suitable programs to make their future virtual-screening events on covalent targets worthwhile and scientifically rational. More interestingly, we went beyond the classical description of the functionality of covalent-docking programs down to selecting the ‘best’ program to consult with during a virtual-screening campaign based on receptor class and covalent warhead chemistry. In addition, we made a highlight on how covalent docking could be achieved using random conventional docking software. And lastly, we raised an alert on the growing erroneous molecular docking practices with covalent targets. Our aim is to guide scientists in the rational docking pursuit when dealing with covalent targets, as this will reduce false-positive results and also increase the reliability of their work for translational research. Graphical abstract

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Section: Features and Applicationsmentioning

confidence: 99%

AroCageDB: A Web-Based Resource for Aromatic Cage Binding Sites and Their Intrinsic Ligands

Moumbock

Qaseem

et al. 2021

J. Chem. Inf. Model.

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While aromatic cages have extensively been investigated in the context of structural biology, molecular recognition, and drug discovery, there exist to date no comprehensive resource for proteins sharing this conserved structural motif. To this end, we parsed the Protein Data Bank and thus constructed the Aromatic Cage Database (AroCageDB), a database for investigating the binding pocket descriptors and ligand binding space of aromatic-cage-containing proteins (ACCPs). AroCageDB contains 487 unique ACCPs bound to 890 unique ligands, for a total of 1636 complexes. This web-accessible database provides a user-friendly interface for the interactive visualization of ligand-bound ACCP structures, with a variety of search options that will open up opportunities for structural analyses and drug discovery campaigns. AroCageDB is freely available at .

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CovPDB: a high-resolution coverage of the covalent protein–ligand interactome

Cited by 26 publications

References 38 publications

IMPPAT 2.0: an enhanced and expanded phytochemical atlas of Indian medicinal plants

IMPPAT 2.0: an enhanced and expanded phytochemical atlas of Indian medicinal plants

Docking covalent targets for drug discovery: stimulating the computer-aided drug design community of possible pitfalls and erroneous practices

AroCageDB: A Web-Based Resource for Aromatic Cage Binding Sites and Their Intrinsic Ligands

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