Fulltext

Molecular dynamics simulations and free energy calculations of netropsin and distamycin binding to an AAAAA DNA binding site

Dolenc, Jožica ; Oostenbrink, Chris ; Koller, Jože ; van Gunsteren, Wilfred F.

In: Nucleic Acids Research, 2005, vol. 33, no. 2, p. 725-733

Ajouter à la liste personnelle
    Titre
    • Molecular dynamics simulations and free energy calculations of netropsin and distamycin binding to an AAAAA DNA binding site
    Auteur
    • Dolenc, Jožica
    • Oostenbrink, Chris. Laboratory of Physical Chemistry, Swiss Federal Institute of Technology ETH-Hönggerberg, CH-8093 Zurich, Switzerland
    • Koller, Jože
    • van Gunsteren, Wilfred F.. Laboratory of Physical Chemistry, Swiss Federal Institute of Technology ETH-Hönggerberg, CH-8093 Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Nucleic Acids Research, 2005, vol. 33, no. 2, p. 725-733. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:293474
    Summary
    Molecular dynamics simulations have been performed on netropsin in two different charge states and on distamycin binding to the minor groove of the DNA duplex d(CGCGAAAAACGCG)·d(CGCGTTTTTCGCG). The relative free energy of binding of the two non-covalently interacting ligands was calculated using the thermodynamic integration method and reflects the experimental result. From 2 ns simulations of the ligands free in solution and when bound to DNA, the mobility and the hydrogen-bonding patterns of the ligands were studied, as well as their hydration. It is shown that even though distamycin is less hydrated than netropsin, the loss of ligand-solvent interactions is very similar for both ligands. The relative mobilities of the ligands in their bound and free forms indicate a larger entropic penalty for distamycin when binding to the minor groove compared with netropsin, partially explaining the lower binding affinity of the distamycin molecule. The detailed structural and energetic insights obtained from the molecular dynamics simulations allow for a better understanding of the factors determining ligand-DNA binding