Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA
DNA is the target of chemical compounds (drugs, pollutants, photosensitizers, etc.), which bind through non-covalent interactions. Depending on their structure and their chemical properties, DNA binders can associate to the minor or to the major groove of double-stranded DNA. They can also intercala...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-01-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/2/228 |
| _version_ | 1818118298049445888 |
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| author | Hong Zhang Hugo Gattuso Elise Dumont Wensheng Cai Antonio Monari Christophe Chipot François Dehez |
| author_facet | Hong Zhang Hugo Gattuso Elise Dumont Wensheng Cai Antonio Monari Christophe Chipot François Dehez |
| author_sort | Hong Zhang |
| collection | DOAJ |
| description | DNA is the target of chemical compounds (drugs, pollutants, photosensitizers, etc.), which bind through non-covalent interactions. Depending on their structure and their chemical properties, DNA binders can associate to the minor or to the major groove of double-stranded DNA. They can also intercalate between two adjacent base pairs, or even replace one or two base pairs within the DNA double helix. The subsequent biological effects are strongly dependent on the architecture of the binding motif. Discriminating between the different binding patterns is of paramount importance to predict and rationalize the effect of a given compound on DNA. The structural characterization of DNA complexes remains, however, cumbersome at the experimental level. In this contribution, we employed all-atom molecular dynamics simulations to determine the standard binding free energy of DNA with netropsin, a well-characterized antiviral and antimicrobial drug, which associates to the minor groove of double-stranded DNA. To overcome the sampling limitations of classical molecular dynamics simulations, which cannot capture the large change in configurational entropy that accompanies binding, we resort to a series of potentials of mean force calculations involving a set of geometrical restraints acting on collective variables. |
| first_indexed | 2024-12-11T04:52:05Z |
| format | Article |
| id | doaj.art-20de9fc1eaf8466db08fdc824998174c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T04:52:05Z |
| publishDate | 2018-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-20de9fc1eaf8466db08fdc824998174c2022-12-22T01:20:21ZengMDPI AGMolecules1420-30492018-01-0123222810.3390/molecules23020228molecules23020228Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNAHong Zhang0Hugo Gattuso1Elise Dumont2Wensheng Cai3Antonio Monari4Christophe Chipot5François Dehez6Research Center for Analytical Sciences, College of Chemistry, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University, Tianjin 300071, ChinaUMR 7019, Theoretical Physics and Chemistry Department (LPCT), Université de Lorraine-Nancy, 54506 Vandoeuvre-lès-Nancy, FranceUniv Lyon, Ens de Lyon, CNRS UMR 5182, Laboratoire de Chimie, Université Claude Bernard Lyon 1, F-69342 Lyon, FranceResearch Center for Analytical Sciences, College of Chemistry, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University, Tianjin 300071, ChinaUMR 7019, Theoretical Physics and Chemistry Department (LPCT), Université de Lorraine-Nancy, 54506 Vandoeuvre-lès-Nancy, FranceUMR 7019, Theoretical Physics and Chemistry Department (LPCT), Université de Lorraine-Nancy, 54506 Vandoeuvre-lès-Nancy, FranceUMR 7019, Theoretical Physics and Chemistry Department (LPCT), Université de Lorraine-Nancy, 54506 Vandoeuvre-lès-Nancy, FranceDNA is the target of chemical compounds (drugs, pollutants, photosensitizers, etc.), which bind through non-covalent interactions. Depending on their structure and their chemical properties, DNA binders can associate to the minor or to the major groove of double-stranded DNA. They can also intercalate between two adjacent base pairs, or even replace one or two base pairs within the DNA double helix. The subsequent biological effects are strongly dependent on the architecture of the binding motif. Discriminating between the different binding patterns is of paramount importance to predict and rationalize the effect of a given compound on DNA. The structural characterization of DNA complexes remains, however, cumbersome at the experimental level. In this contribution, we employed all-atom molecular dynamics simulations to determine the standard binding free energy of DNA with netropsin, a well-characterized antiviral and antimicrobial drug, which associates to the minor groove of double-stranded DNA. To overcome the sampling limitations of classical molecular dynamics simulations, which cannot capture the large change in configurational entropy that accompanies binding, we resort to a series of potentials of mean force calculations involving a set of geometrical restraints acting on collective variables.http://www.mdpi.com/1420-3049/23/2/228binding free energyDNA sensitizationnetropsinall-atom molecular dynamicsminor-groove binder |
| spellingShingle | Hong Zhang Hugo Gattuso Elise Dumont Wensheng Cai Antonio Monari Christophe Chipot François Dehez Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA Molecules binding free energy DNA sensitization netropsin all-atom molecular dynamics minor-groove binder |
| title | Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA |
| title_full | Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA |
| title_fullStr | Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA |
| title_full_unstemmed | Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA |
| title_short | Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA |
| title_sort | accurate estimation of the standard binding free energy of netropsin with dna |
| topic | binding free energy DNA sensitization netropsin all-atom molecular dynamics minor-groove binder |
| url | http://www.mdpi.com/1420-3049/23/2/228 |
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