On the Molecular Mechanism of Drug Intercalation into DNA: A Simulation Study of the Intercalation Pathway, Free Energy, and DNA Structural Changes

Mukherjee, Arnab; Lavery, Richard; Bagchi, Biman; Hynes, James T.

doi:10.1021/ja8001666

Cited by 180 publications

(227 citation statements)

References 78 publications

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“…Although it last for about 2 ns, intercalation did not occur. This observed behavior is consistent with a mechanism of intercalation similar to the proposed by Mukherjee et al 39 for the case of daunomycin. According to this mechanism, there is a previous minor groove-bound state which is separated from the intercalated state by a free energy barrier of about 12 kcal mol -1 .…”

Section: Intercalation Complex Of Symmetric Tröger Base (Sym-int)supporting

confidence: 91%

Simulation of the interactions between Tröger bases and DNA

Ricci¹,

Netz²

2012

J. Braz. Chem. Soc.

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Section: Intercalation Complex Of Symmetric Tröger Base (Sym-int)supporting

confidence: 91%

Simulation of the interactions between Tröger bases and DNA

Ricci¹,

Netz²

2012

J. Braz. Chem. Soc.

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“…14 Finally, in a more clearly dynamical vein, water hydration shell rearrangement has been implicated as a key ingredient for the intercalation (insertion) of anti-cancer drugs into the DNA minor groove. 15 Heat protection. Most biomolecules are only active in one specific structure, e.g.…”

Section: Why Is Water Dynamics Next To a Biomolecule Important For Itmentioning

confidence: 99%

Biomolecular hydration dynamics: a jump model perspective

et al. 2013

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The dynamics of water molecules within the hydration shell surrounding a biomolecule can have a crucial influence on its biochemical function. Characterizing their properties and the extent to which they differ from those of bulk water have thus been long-standing questions. Following a tutorial approach, we review the recent advances in this field and the different approaches which have probed the dynamical perturbation experienced by water in the vicinity of proteins or DNA. We discuss the molecular factors causing this perturbation, and describe how they change with temperature. We finally present more biologically relevant cases beyond the dilute aqueous situation. A special focus is on the jump model for water reorientation and hydrogen bond rearrangement.

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“…This could be either-for me, the boring option-an equilibrium phenomenon in which the drug would sit just outside the DNA and simply wait until an equilibrium fluctuation allowed it to enter or-in my view, the more exciting scenario-a dynamic phenomenon in which the drug would force its way in, coupled to the DNA dynamics along the way. After an approximately three-decade hiatus, we finally examined the intercalation of the anticancer drug daunomycin into DNA with postdoc Arnab Mukherjee and colleagues Bagchi, Richard Lavery, and Krystyna Zakrzewska (146,147). We could see some of the key DNA, water solvent, and drug motions necessary for the intercalation in a scenario that suggested the aggressive rather than the passive role for the drug.…”

Section: Atmospheric Interstellar Biological and Renewable Energy mentioning

confidence: 99%

Molecules in Motion: Chemical Reaction and Allied Dynamics in Solution and Elsewhere

Hynes

2015

Annu. Rev. Phys. Chem.

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After my acceptance of the kind invitation from Todd Martínez and Mark Johnson, Co-Editors of this journal, to write this article, I had to decide just how to actually do this, given the existence of a fairly personal and extended autobiographical account of recent vintage detailing my youth, education, and assorted experiences and activities at the University of Colorado, Boulder, and later also at Ecole Normale Supérieure in Paris (1). In the end, I settled on a differently styled recounting of the adventures with my students, postdocs, collaborators, and colleagues in trying to unravel, comprehend, describe, and occasionally even predict the manifestations and consequences of the myriad assortment of molecular dances that contribute to and govern the rates and mechanisms of chemical reactions in solution (and elsewhere TRANSLATIONAL, ROTATIONAL, AND SOLVATION DYNAMICS IN SOLUTIONThis is basically where it all began for me. Beyond their fundamental interest, these three types of dynamics (translational, rotational, and solvation) can be important for chemical reactions in assorted regimes, although admittedly this is perhaps not always so obvious: Translation is relevant for diffusion-controlled and -influenced reactions, water rotation is important for proton transfers (PTs), for example, and solvation dynamics can have a significant effect on any reaction involving the redistribution or rearrangement of charges. I give only brief commentaries on our work at the University of Colorado, Boulder, on these types of dynamics in the 1970s and 1980s and end with more recent aspects carried out at Ecole Normal Supérieure (ENS).In the 1970s, it was thought by not a few that macroscopic continuum hydrodynamics-as reflected in, e.g., Stokes' friction laws for translation and rotation, the Stokes-Einstein equation for translational diffusion, and the Debye-Stokes-Einstein relation for rotational or reorientational diffusion-could actually apply in detail, and even quantitatively, at a molecular level. I myself have used (and continue to use) continuum hydrodynamic and dielectric models to provide concepts, perspectives, and guides for experiment. Clearly, I like such models greatly, but I just could not accept going this far. Together with Mike Weinberg and Ray Kapral (2-4), we addressed the issue with what we called a microscopic boundary layer approach, combining a molecular collisional picture for the immediate solvent neighborhood of a rotating or translating solute molecule with a hydrodynamic description of the remaining, outer solvent. We showed that for both rotational and translational friction (and thus for diffusion), the molecular aspects were indeed dominant. Although hydrodynamic influences could also enter, they only became the dominant story when the solute was far larger than the solvent molecules. We also found that the supposed agreement of assorted simulations and experiments with the hydrodynamic view disappeared upon suitable scrutiny. Solvation DynamicsThis flavor of dynamics came into it...

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On the Molecular Mechanism of Drug Intercalation into DNA: A Simulation Study of the Intercalation Pathway, Free Energy, and DNA Structural Changes

Cited by 180 publications

References 78 publications

Simulation of the interactions between Tröger bases and DNA

Simulation of the interactions between Tröger bases and DNA

Biomolecular hydration dynamics: a jump model perspective

Molecules in Motion: Chemical Reaction and Allied Dynamics in Solution and Elsewhere

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