Novel virtual screening protocol based on the combined use of molecular modeling and electron-ion interaction potential techniques to design HIV-1 integrase inhibitors
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Аутори
Tintori, CristinaManetti, Fabrizio
Veljković, Nevena V.
Perović, Vladimir R.
Vercammen, Jo
Hayes, Sean
Massa, Silvio
Witvrouw, Myriam
Debyser, Zeger
Veljković, Veljko
Botta, Maurizio
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HIV-1 integrase (IN) is an essential enzyme for viral replication and represents an intriguing target for the development of new drugs. Although a large number of compounds have been reported to inhibit IN in biochemical assays, no drug active against this enzyme has been approved by the FDA so far. In this study, we report, for the first time, the use of the electron-ion interaction potential (EIIP) technique in combination with molecular modeling approaches for the identification of new IN inhibitors. An innovative virtual screening approach, based on the determination of both short- and long-range interactions between interacting molecules, was employed with the aim of identifying molecules able to inhibit the binding of IN to viral DNA. Moreover, results from a database screening on the commercial Asinex Gold Collection led to the selection of several compounds. One of them showed a significant inhibitory potency toward IN in the overall integration assay. Biological investigations... also showed, in agreement with modeling studies, that these compounds prevent recognition of DNA by IN in a fluorescence fluctuation assay, probably by interacting with the DNA binding domain of IN.
Извор:
Journal of Chemical Information and Modeling, 2007, 47, 4, 1536-1544
DOI: 10.1021/ci700078n
ISSN: 1549-9596
PubMed: 17608406
WoS: 000248192200025
Scopus: 2-s2.0-34547692844
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Институција/група
VinčaTY - JOUR AU - Tintori, Cristina AU - Manetti, Fabrizio AU - Veljković, Nevena V. AU - Perović, Vladimir R. AU - Vercammen, Jo AU - Hayes, Sean AU - Massa, Silvio AU - Witvrouw, Myriam AU - Debyser, Zeger AU - Veljković, Veljko AU - Botta, Maurizio PY - 2007 UR - https://vinar.vin.bg.ac.rs/handle/123456789/3226 AB - HIV-1 integrase (IN) is an essential enzyme for viral replication and represents an intriguing target for the development of new drugs. Although a large number of compounds have been reported to inhibit IN in biochemical assays, no drug active against this enzyme has been approved by the FDA so far. In this study, we report, for the first time, the use of the electron-ion interaction potential (EIIP) technique in combination with molecular modeling approaches for the identification of new IN inhibitors. An innovative virtual screening approach, based on the determination of both short- and long-range interactions between interacting molecules, was employed with the aim of identifying molecules able to inhibit the binding of IN to viral DNA. Moreover, results from a database screening on the commercial Asinex Gold Collection led to the selection of several compounds. One of them showed a significant inhibitory potency toward IN in the overall integration assay. Biological investigations also showed, in agreement with modeling studies, that these compounds prevent recognition of DNA by IN in a fluorescence fluctuation assay, probably by interacting with the DNA binding domain of IN. T2 - Journal of Chemical Information and Modeling T1 - Novel virtual screening protocol based on the combined use of molecular modeling and electron-ion interaction potential techniques to design HIV-1 integrase inhibitors VL - 47 IS - 4 SP - 1536 EP - 1544 DO - 10.1021/ci700078n ER -
@article{ author = "Tintori, Cristina and Manetti, Fabrizio and Veljković, Nevena V. and Perović, Vladimir R. and Vercammen, Jo and Hayes, Sean and Massa, Silvio and Witvrouw, Myriam and Debyser, Zeger and Veljković, Veljko and Botta, Maurizio", year = "2007", abstract = "HIV-1 integrase (IN) is an essential enzyme for viral replication and represents an intriguing target for the development of new drugs. Although a large number of compounds have been reported to inhibit IN in biochemical assays, no drug active against this enzyme has been approved by the FDA so far. In this study, we report, for the first time, the use of the electron-ion interaction potential (EIIP) technique in combination with molecular modeling approaches for the identification of new IN inhibitors. An innovative virtual screening approach, based on the determination of both short- and long-range interactions between interacting molecules, was employed with the aim of identifying molecules able to inhibit the binding of IN to viral DNA. Moreover, results from a database screening on the commercial Asinex Gold Collection led to the selection of several compounds. One of them showed a significant inhibitory potency toward IN in the overall integration assay. Biological investigations also showed, in agreement with modeling studies, that these compounds prevent recognition of DNA by IN in a fluorescence fluctuation assay, probably by interacting with the DNA binding domain of IN.", journal = "Journal of Chemical Information and Modeling", title = "Novel virtual screening protocol based on the combined use of molecular modeling and electron-ion interaction potential techniques to design HIV-1 integrase inhibitors", volume = "47", number = "4", pages = "1536-1544", doi = "10.1021/ci700078n" }
Tintori, C., Manetti, F., Veljković, N. V., Perović, V. R., Vercammen, J., Hayes, S., Massa, S., Witvrouw, M., Debyser, Z., Veljković, V.,& Botta, M.. (2007). Novel virtual screening protocol based on the combined use of molecular modeling and electron-ion interaction potential techniques to design HIV-1 integrase inhibitors. in Journal of Chemical Information and Modeling, 47(4), 1536-1544. https://doi.org/10.1021/ci700078n
Tintori C, Manetti F, Veljković NV, Perović VR, Vercammen J, Hayes S, Massa S, Witvrouw M, Debyser Z, Veljković V, Botta M. Novel virtual screening protocol based on the combined use of molecular modeling and electron-ion interaction potential techniques to design HIV-1 integrase inhibitors. in Journal of Chemical Information and Modeling. 2007;47(4):1536-1544. doi:10.1021/ci700078n .
Tintori, Cristina, Manetti, Fabrizio, Veljković, Nevena V., Perović, Vladimir R., Vercammen, Jo, Hayes, Sean, Massa, Silvio, Witvrouw, Myriam, Debyser, Zeger, Veljković, Veljko, Botta, Maurizio, "Novel virtual screening protocol based on the combined use of molecular modeling and electron-ion interaction potential techniques to design HIV-1 integrase inhibitors" in Journal of Chemical Information and Modeling, 47, no. 4 (2007):1536-1544, https://doi.org/10.1021/ci700078n . .