Molecular Dynamics Insights into Polyamine-DNA Binding Modes: Implications for Cross-Link Selectivity

Abstract : Biogenic polyamines, which play a role in DNA condensation and stabilization, are ubiquitous and are found at millimolar concentration in the nucleus of eukaryotic cells. The interaction modes of three polyamines-putrescine (Put), spermine (Spm), and spermidine (Spd)-with a self-complementary 16 base pair (bp) duplex, are investigated by all-atom explicit-solvent molecular dynamics. The length of the amine aliphatic chain leads to a change of the interaction mode from minor groove binding to major groove binding. Through all-atom dynamics, noncovalent interactions that stabilize the polyamine-DNA complex and prefigure the reactivity, leading to the low-barrier formation of deleterious DNA-polyamine cross-links, after one-electron oxidation of a guanine nucleobase, are unraveled. The binding strength is quantified from the obtained trajectories by molecular mechanics generalized Born surface area post-processing (MM-GBSA). The values of binding free energies provide the same affinity order, Put
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Submitted on : Thursday, November 23, 2017 - 2:09:18 PM
Last modification on : Thursday, April 4, 2019 - 5:10:03 PM

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Emmanuelle Bignon, Chen-Hui Chan, Christophe Morell, Antonio Monari, Jean-Luc Ravanat, et al.. Molecular Dynamics Insights into Polyamine-DNA Binding Modes: Implications for Cross-Link Selectivity. Chemistry - A European Journal, Wiley-VCH Verlag, 2017, 23 (52), pp.12845-12852. ⟨10.1002/chem.201702065⟩. ⟨hal-01646327⟩

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