Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA

被引:15
|
作者
Zhang, Hong [1 ]
Gattuso, Hugo [2 ,3 ]
Dumont, Elise [4 ]
Cai, Wensheng [1 ,5 ]
Monari, Antonio [2 ,3 ]
Chipot, Christophe [2 ,3 ,6 ,7 ,8 ]
Dehez, Francois [2 ,3 ,6 ,7 ]
机构
[1] Nankai Univ, Coll Chem, Tianjin Key Lab Biosensing & Mol Recognit, Res Ctr Analyt Sci, Tianjin 300071, Peoples R China
[2] Univ Lorraine Nancy, Theoret Phys & Chem Dept LPCT, UMR 7019, F-54506 Vandoeuvre Les Nancy, France
[3] CNRS, Theoret Phys & Chem Dept LPCT, UMR 7019, F-54506 Vandoeuvre Les Nancy, France
[4] Univ Claude Bernard Lyon 1, Univ Lyon, CNRS, Ens Lyon,UMR 5182,Lab Chim, F-69342 Lyon, France
[5] Nankai Univ, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China
[6] CNRS, Lab Int Associe, F-54506 Vandoeuvre Les Nancy, France
[7] Univ Illinois, Champaign, IL 61820 USA
[8] Univ Illinois, Dept Phys, 1110 West Green St, Urbana, IL 61801 USA
来源
MOLECULES | 2018年 / 23卷 / 02期
关键词
binding free energy; DNA sensitization; netropsin; all-atom molecular dynamics; minor-groove binder; BIOLOGICAL CONSEQUENCES; MOLECULAR-DYNAMICS; OXIDATIVE STRESS; CELLULAR-DNA; NUCLEIC-ACIDS; NILE BLUE; DAMAGE; PHOTOSENSITIZATION; BENZOPHENONE; SIMULATIONS;
D O I
10.3390/molecules23020228
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:15
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