TY  - JOUR
AU  - Tintori, Cristina
AU  - Veljković, Nevena V.
AU  - Veljković, Veljko
AU  - Botta, Maurizio
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4144
AB  - A crystal structure of the integrase binding domain (IBD) of the lens epithelium-derived growth factor (LEDGF/p75) in complex with the dimer of the HIV-1 integrase (IN) catalytic core domain (CCD) provides useful information that might help in the understanding of essential protein-protein contacts in HIV-1. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. On the other hand, the biochemical characterization of the interaction between full-length IN and LEDGF/p75 has recently proved that LEDGF/p75 promotes IN tetramerization with two LEDGF/p75 IBD molecules bound to the IN tetramer. This experimental evidence suggests that to obtain a complete structural description of the interactions between the two proteins, the full-length tetrameric structure of IN should be considered. Our aim was to obtain a detailed picture of HIV-1 IN interactions with cellular co-factors that was of general interest, particularly for the development of small molecule IN inhibitors, which mimic the IBD of LEDGF/p75. To this end, we performed bioinformatics analyses to identify protein sequence domains involved in long-range recognition. Subsequently, we applied molecular dynamics techniques to investigate the detailed interactions between the complete tetrameric form of IN and two molecules of the IBD of LEDGF/p75. Our dynamic picture is in agreement with experimental data and, thereby, provides new details of the IN-LEDGF/p75 interaction.
T2  - Proteins: Structure Function and Bioinformatics
T1  - Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method
VL  - 78
IS  - 16
SP  - 3396
EP  - 3408
DO  - 10.1002/prot.22847
ER  - 

@article{
author = "Tintori, Cristina and Veljković, Nevena V. and Veljković, Veljko and Botta, Maurizio",
year = "2010",
abstract = "A crystal structure of the integrase binding domain (IBD) of the lens epithelium-derived growth factor (LEDGF/p75) in complex with the dimer of the HIV-1 integrase (IN) catalytic core domain (CCD) provides useful information that might help in the understanding of essential protein-protein contacts in HIV-1. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. On the other hand, the biochemical characterization of the interaction between full-length IN and LEDGF/p75 has recently proved that LEDGF/p75 promotes IN tetramerization with two LEDGF/p75 IBD molecules bound to the IN tetramer. This experimental evidence suggests that to obtain a complete structural description of the interactions between the two proteins, the full-length tetrameric structure of IN should be considered. Our aim was to obtain a detailed picture of HIV-1 IN interactions with cellular co-factors that was of general interest, particularly for the development of small molecule IN inhibitors, which mimic the IBD of LEDGF/p75. To this end, we performed bioinformatics analyses to identify protein sequence domains involved in long-range recognition. Subsequently, we applied molecular dynamics techniques to investigate the detailed interactions between the complete tetrameric form of IN and two molecules of the IBD of LEDGF/p75. Our dynamic picture is in agreement with experimental data and, thereby, provides new details of the IN-LEDGF/p75 interaction.",
journal = "Proteins: Structure Function and Bioinformatics",
title = "Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method",
volume = "78",
number = "16",
pages = "3396-3408",
doi = "10.1002/prot.22847"
}

Tintori, C., Veljković, N. V., Veljković, V.,& Botta, M.. (2010). Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method. in Proteins: Structure Function and Bioinformatics, 78(16), 3396-3408.
https://doi.org/10.1002/prot.22847

Tintori C, Veljković NV, Veljković V, Botta M. Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method. in Proteins: Structure Function and Bioinformatics. 2010;78(16):3396-3408.
doi:10.1002/prot.22847 .

Tintori, Cristina, Veljković, Nevena V., Veljković, Veljko, Botta, Maurizio, "Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method" in Proteins: Structure Function and Bioinformatics, 78, no. 16 (2010):3396-3408,
https://doi.org/10.1002/prot.22847 . .

TY  - JOUR
AU  - Veljković, Nevena V.
AU  - Glišić, Sanja
AU  - Prljić, Jelena
AU  - Perović, Vladimir R.
AU  - Botta, Maurizio
AU  - Veljković, Veljko
PY  - 2008
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3544
AB  - The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. Here we review the application of the informational spectrum method ( ISM), a virtual spectroscopy method for structure/function analysis of proteins, in identification of functional protein domains representing candidate therapeutic targets for drugs against human immunodeficiency virus (HIV)-1, anthrax, highly pathogenic influenza virus H5N1 and cardiovascular diseases.
T2  - Current Protein and Peptide Science
T1  - Discovery of New Therapeutic Targets by the Informational Spectrum Method
VL  - 9
IS  - 5
SP  - 493
EP  - 506
DO  - 10.2174/138920308785915245
ER  - 

@article{
author = "Veljković, Nevena V. and Glišić, Sanja and Prljić, Jelena and Perović, Vladimir R. and Botta, Maurizio and Veljković, Veljko",
year = "2008",
abstract = "The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. Here we review the application of the informational spectrum method ( ISM), a virtual spectroscopy method for structure/function analysis of proteins, in identification of functional protein domains representing candidate therapeutic targets for drugs against human immunodeficiency virus (HIV)-1, anthrax, highly pathogenic influenza virus H5N1 and cardiovascular diseases.",
journal = "Current Protein and Peptide Science",
title = "Discovery of New Therapeutic Targets by the Informational Spectrum Method",
volume = "9",
number = "5",
pages = "493-506",
doi = "10.2174/138920308785915245"
}

Veljković, N. V., Glišić, S., Prljić, J., Perović, V. R., Botta, M.,& Veljković, V.. (2008). Discovery of New Therapeutic Targets by the Informational Spectrum Method. in Current Protein and Peptide Science, 9(5), 493-506.
https://doi.org/10.2174/138920308785915245

Veljković NV, Glišić S, Prljić J, Perović VR, Botta M, Veljković V. Discovery of New Therapeutic Targets by the Informational Spectrum Method. in Current Protein and Peptide Science. 2008;9(5):493-506.
doi:10.2174/138920308785915245 .

Veljković, Nevena V., Glišić, Sanja, Prljić, Jelena, Perović, Vladimir R., Botta, Maurizio, Veljković, Veljko, "Discovery of New Therapeutic Targets by the Informational Spectrum Method" in Current Protein and Peptide Science, 9, no. 5 (2008):493-506,
https://doi.org/10.2174/138920308785915245 . .

TY  - 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 . .

TY  - JOUR
AU  - Mugnaini, Claudia
AU  - Rajamaki, Suvi
AU  - Tintori, Cristina
AU  - Corelli, Federico
AU  - Massa, Silivio
AU  - Witvrouw, Myriam
AU  - Debyser, Zeger
AU  - Veljković, Veljko
AU  - Botta, Maurizio
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3297
AB  - The identification of a novel hit compound as integrase binding inhibitor has been accomplished by means of virtual screening techniques. A small family of structurally related molecules has been synthesized and biologically evaluated with one of the compounds showing an IC50 = 12 mu M (C) 2007 Elsevier Ltd. All rights reserved.
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - Toward novel HIV-1 integrase binding inhibitors: Molecular modeling, synthesis, and biological studies
VL  - 17
IS  - 19
SP  - 5370
EP  - 5373
DO  - 10.1016/j.bmcl.2007.08.005
ER  - 

@article{
author = "Mugnaini, Claudia and Rajamaki, Suvi and Tintori, Cristina and Corelli, Federico and Massa, Silivio and Witvrouw, Myriam and Debyser, Zeger and Veljković, Veljko and Botta, Maurizio",
year = "2007",
abstract = "The identification of a novel hit compound as integrase binding inhibitor has been accomplished by means of virtual screening techniques. A small family of structurally related molecules has been synthesized and biologically evaluated with one of the compounds showing an IC50 = 12 mu M (C) 2007 Elsevier Ltd. All rights reserved.",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "Toward novel HIV-1 integrase binding inhibitors: Molecular modeling, synthesis, and biological studies",
volume = "17",
number = "19",
pages = "5370-5373",
doi = "10.1016/j.bmcl.2007.08.005"
}

Mugnaini, C., Rajamaki, S., Tintori, C., Corelli, F., Massa, S., Witvrouw, M., Debyser, Z., Veljković, V.,& Botta, M.. (2007). Toward novel HIV-1 integrase binding inhibitors: Molecular modeling, synthesis, and biological studies. in Bioorganic and Medicinal Chemistry Letters, 17(19), 5370-5373.
https://doi.org/10.1016/j.bmcl.2007.08.005

Mugnaini C, Rajamaki S, Tintori C, Corelli F, Massa S, Witvrouw M, Debyser Z, Veljković V, Botta M. Toward novel HIV-1 integrase binding inhibitors: Molecular modeling, synthesis, and biological studies. in Bioorganic and Medicinal Chemistry Letters. 2007;17(19):5370-5373.
doi:10.1016/j.bmcl.2007.08.005 .

Mugnaini, Claudia, Rajamaki, Suvi, Tintori, Cristina, Corelli, Federico, Massa, Silivio, Witvrouw, Myriam, Debyser, Zeger, Veljković, Veljko, Botta, Maurizio, "Toward novel HIV-1 integrase binding inhibitors: Molecular modeling, synthesis, and biological studies" in Bioorganic and Medicinal Chemistry Letters, 17, no. 19 (2007):5370-5373,
https://doi.org/10.1016/j.bmcl.2007.08.005 . .