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Molecules 2018, 23(2), 228; https://doi.org/10.3390/molecules23020228

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

1
Research Center for Analytical Sciences, College of Chemistry, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University, Tianjin 300071, China
2
UMR 7019, Theoretical Physics and Chemistry Department (LPCT), Université de Lorraine-Nancy, 54506 Vandoeuvre-lès-Nancy, France
3
UMR 7019, Theoretical Physics and Chemistry Department (LPCT), CNRS, 54506 Vandeouvre-lès-Nancy, France
4
Univ Lyon, Ens de Lyon, CNRS UMR 5182, Laboratoire de Chimie, Université Claude Bernard Lyon 1, F-69342 Lyon, France
5
Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China
6
Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Champaign, Illinois, 54506 Vandeouvre-lès-Nancy, France
7
Department of Physics, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, IL 61801, USA
*
Author to whom correspondence should be addressed.
Received: 23 December 2017 / Revised: 14 January 2018 / Accepted: 19 January 2018 / Published: 25 January 2018
(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)
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Abstract

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. View Full-Text
Keywords: binding free energy; DNA sensitization; netropsin; all-atom molecular dynamics; minor-groove binder binding free energy; DNA sensitization; netropsin; all-atom molecular dynamics; minor-groove binder
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Zhang, H.; Gattuso, H.; Dumont, E.; Cai, W.; Monari, A.; Chipot, C.; Dehez, F. Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA. Molecules 2018, 23, 228.

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