Use of the parmbsc0 force field and trajectory analysis to study the binding of netropsin to the DNA fragment (5′CCAATTGG)2 in the presence of excess NaCl salt in aqueous solution

Andac, Cenk A.; Miandji, Anooshirvan M.; Hornemann, Ulfert; Noyanalpan, Ningur

doi:10.1016/j.ijbiomac.2011.02.004

Cited by 6 publications

(4 citation statements)

References 44 publications

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“…Yet, the dynamic adjustments of the intercalated drug-DNA complex in the latter steps could not be obtained from this equilibrium thermodynamics methodology, and the detailed intercalation process at atomic level remains elusive. In addition, the validity of AMBER DNA force field [17] in drug-DNA binding simulation [18] remains to be established.…”

Section: Introductionmentioning

confidence: 99%

Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations

Lei

Wang

2012

Journal of Molecular Graphics and Modelling

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Section: Introductionmentioning

confidence: 99%

Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations

Lei

Wang

2012

Journal of Molecular Graphics and Modelling

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“…Optimization of melting measurements for tethered duplexes is described, and the approach is used to determine thermodynamics of binding between a model compound, netropsin (Net), and its DNA recognition site. Net is a minor-groove binder with high specificity for double-stranded DNA sequences rich in adenine-thymine base pairs , whose fundamental properties continue to be investigated, − although toxicity renders it unsuitable for clinical use . Net-DNA interactions are studied as a function of ionic strength and ligand concentration by electrochemically monitoring melting transitions of immobilized duplexes.…”

Section: Introductionmentioning

confidence: 99%

Melting Thermodynamics of Reversible DNA/Ligand Complexes at Interfaces

Belozerova

Levicky

2012

J. Am. Chem. Soc.

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A variety of solution methods exist for analysis of interactions between small molecule ligands and nucleic acids; however, accomplishing this task economically at the scale of hundreds to thousands of sequences remains challenging. Surface assays offer a prospective solution through array-based multiplexing, capable of mapping out the full sequence context of a DNA/ligand interaction in a single experiment. However, relative to solution assays, accurate quantification of DNA/ligand interactions in a surface format must contend with limited understanding of molecular activities and interactions at a solid-liquid interface. We report a surface adaptation of a solution method in which shifts in duplex stability, induced by ligand binding and quantified from melting transitions, are used for thermodynamic analysis of DNA/ligand interactions. The results are benchmarked against solution calorimetric data. Equilibrium operation is confirmed through superposition of denaturation/hybridization transitions triggered by heating and cooling. The antibiotic compound netropsin, which undergoes electrostatic and sequence-specific minor groove interactions with DNA, is used as a prototypical small molecule. DNA/netropsin interactions are investigated as a function of ionic strength and drug concentration through electrochemical tracing of surface melt transitions. Comparison with solution values finds excellent agreement in free energy, though reliable separation into enthalpic and entropic contributions proves more difficult. The results establish key guidelines for analysis of DNA-ligand interactions via reversible melting denaturation at surfaces.

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“…They made changes for correct representation of the α/γ concerted rotation in nucleic acids. Many of the previously performed studies were repeated using this well developed and validated force field; one of them was for Netropsin using parmbsc0 force field (Andac et al, 2011). Recently, Ascona B-DNA Consortium broke the microsecond barriers in B-DNA simulation using parmbs0, giving a clear view on B-DNA behavior in long-run MD simulations (Beveridge et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulation studies for DNA sequence recognition by reactive metabolites of anticancer compounds

Tumbi

Nandekar

Shaikh

et al. 2014

J of Molecular Recognition

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The discovery of novel anticancer molecules 5F-203 (NSC703786) and 5-aminoflavone (5-AMF, NSC686288) has addressed the issues of toxicity and reduced efficacy by targeting over expressed Cytochrome P450 1A1 (CYP1A1) in cancer cells. CYP1A1 metabolizes these compounds into their reactive metabolites, which are proven to mediate their anticancer effect through DNA adduct formation. However, the drug metabolite-DNA binding has not been explored so far. Hence, understanding the binding characteristics and molecular recognition for drug metabolites with DNA is of practical and fundamental interest. The present study is aimed to model binding preference shown by reactive metabolites of 5F-203 and 5-AMF with DNA in forming DNA adducts. To perform this, three different DNA crystal structures covering sequence diversity were selected, and 12 DNA-reactive metabolite complexes were generated. Molecular dynamics simulations for all complexes were performed using AMBER 11 software after development of protocol for DNA-reactive metabolite system. Furthermore, the MM-PBSA/GBSA energy calculation, per-nucleotide energy decomposition, and Molecular Electrostatic Surface Potential analysis were performed. The results obtained from present study clearly indicate that minor groove in DNA is preferable for binding of reactive metabolites of anticancer compounds. The binding preferences shown by reactive metabolites were also governed by specific nucleotide sequence and distribution of electrostatic charges in major and minor groove of DNA structure. Overall, our study provides useful insights into the initial step of mechanism of reactive metabolite binding to the DNA and the guidelines for designing of sequence specific DNA interacting anticancer agents.

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Use of the parmbsc0 force field and trajectory analysis to study the binding of netropsin to the DNA fragment (5′CCAATTGG)2 in the presence of excess NaCl salt in aqueous solution

Cited by 6 publications

References 44 publications

Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations

Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations

Melting Thermodynamics of Reversible DNA/Ligand Complexes at Interfaces

Molecular dynamics simulation studies for DNA sequence recognition by reactive metabolites of anticancer compounds

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