Dynamical Treatment of Charge Transfer through Duplex Nucleic Acids Containing Modified Adenines

Brancolini, Giorgia; Migliore, Agostino; Corni, Stefano; Fuentes‐Cabrera, Miguel; Luque, F. Javier; Felice, Rosa Di

doi:10.1021/nn404165y

Cited by 8 publications

(6 citation statements)

References 72 publications

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“…Figures S7−S10, along with Figure 9, report more information on the quantities summarized in Table 2. In agreement with other studies on the structure dependence of the electronic properties of nucleic acids, 19,21,37,84,85 we detect a remarkable variability of the excited-state electronic properties monitored in this work. This variability is potentially a basis to realize tunable molecular wires based on sequence/structure design.…”

Section: Electric Dipole Momentsupporting

confidence: 93%

Effects of Structural Dynamics on Charge Carrier Transfer in B-DNA: A Combined MD and RT-TDDFT Study

et al. 2021

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Hole transfer along the axis of duplex DNA has been the focus of physical chemistry research for decades, with implications in diverse fields, from nanotechnology to cell oxidative damage. Computational approaches are particularly amenable for this problem, to complement experimental data for interpretation of transfer mechanisms. To be predictive, computational results need to account for the inherent mobility of biological molecules during the time frame of experimental measurements. Here, we address the structural variability of B-DNA and its effects on hole transfer in a combined molecular dynamics (MD) and real-time time-dependent density functional theory (RT-TDDFT) study. Our results show that quantities that characterize the charge transfer process, such as the time-dependent dipole moment and hole population at a specific site, are sensitive to structural changes that occur on the nanosecond time scale. We extend the range of physical properties for which such a correlation has been observed, further establishing the fact that quantitative computational data on charge transfer properties should include statistical averages. Furthermore, we use the RT-TDDFT results to assess an efficient tight-binding method suitable for high-throughput predictions. We demonstrate that charge transfer, although affected by structural variability, on average, remains strong in AA and GG dimers.

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Section: Electric Dipole Momentsupporting

confidence: 93%

Effects of Structural Dynamics on Charge Carrier Transfer in B-DNA: A Combined MD and RT-TDDFT Study

et al. 2021

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“…Before starting the T-REMD, we applied to both systems an equilibration protocol which consists of various steps of optimization of atomic coordinates and restrained finite-temperature dynamics during which the restraints on protein atoms were gradually weakened and eventually released, according to a previously reported procedure. − At the end of the equilibration, the trajectories were stable in terms of density, temperature, potential energy, and other macroscopic properties. The equilibration phases of the nonprotonated and protonated protein were followed by 20 ns of unrestrained T-REMD in which 32 replicas on the top of the cit-Au(111) surface for each system were used, yielding an aggregated simulation time of 640 ns.…”

Section: Resultsmentioning

confidence: 99%

Probing the Influence of Citrate-Capped Gold Nanoparticles on an Amyloidogenic Protein

et al. 2015

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Nanoparticles (NPs) are known to exhibit distinct physical and chemical properties compared with the same materials in bulk form. NPs have been repeatedly reported to interact with proteins, and this interaction can be exploited to affect processes undergone by proteins, such as fibrillogenesis. Fibrillation is common to many proteins, and in living organisms, it causes tissue-specific or systemic amyloid diseases. The nature of NPs and their surface chemistry is crucial in assessing their affinity for proteins and their effects on them. Here we present the first detailed structural characterization and molecular mechanics model of the interaction between a fibrillogenic protein, β2-microglobulin, and a NP, 5 nm hydrophilic citrate-capped gold nanoparticles. NMR measurements and simulations at multiple levels (enhanced sampling molecular dynamics, Brownian dynamics, and Poisson-Boltzmann electrostatics) explain the origin of the observed protein perturbations mostly localized at the amino-terminal region. Experiments show that the protein-NP interaction is weak in the physiological-like, conditions and do not induce protein fibrillation. Simulations reproduce these findings and reveal instead the role of the citrate in destabilizing the lower pH protonated form of β2-microglobulin. The results offer possible strategies for controlling the desired effect of NPs on the conformational changes of the proteins, which have significant roles in the fibrillation process.

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“…Understanding the molecular basis of the interaction between DNA and small binders is of fundamental interest for the rational design of new therapeutic agents 1,2 and developments in DNA-based nano technologies. [3][4][5] Our current understanding of the molecular recognition between biomolecules and druglike binders involves a dynamic process where the molecular partners undergo structural and dynamical adaptation to promote binding and unbinding events. [6][7][8][9][10][11] The central role of molecular flexibility in ligand-receptor interaction is now well recognized, 9,10,12 and dynamical modifications occurring upon binding have their thermodynamical counterpart in the entropic factors contributing to the overall binding free energy.…”

Section: Introductionmentioning

confidence: 99%

Atomistic account of structural and dynamical changes induced by small binders in the double helix of a short DNA

Fresch

Remacle

2014

Phys. Chem. Chem. Phys.

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Nucleic acids are flexible molecules and their dynamical properties play a key role in molecular recognition events. Small binders interacting with DNA fragments induce both structural and dynamical changes in the double helix. We study the dynamics of a DNA dodecamer and of its complexes with Hoechst 33258, which is a minor groove binder, and with the ethidium cation, which is an intercalator, by molecular dynamics simulation. The thermodynamics of DNA-drug interaction is evaluated in connection with the structure and the dynamics of the resulting complexes. We identify and characterize the relevant changes in the configurational distribution of the DNA helix and relate them to the corresponding entropic contributions to the binding free energy. The binder Hoechst locks the breathing motion of the minor groove inducing a reduction of the configurational entropy of the helix, which amounts to 20 kcal mol(-1). In contrast, intercalations with the ethidium cation enhance the flexibility of the double helix. We show that the balance between the energy required to deform the helix for the intercalation and the gain in configurational entropy is the origin of cooperativity in the binding of a second ethidium and of anti-cooperativity in the binding of a third one. The results of our study provide an understanding of the relation between structure, dynamics and energetics in the interaction between DNA fragments and small binders, highlighting the role of dynamical changes and consequent variation of the configurational entropy of the DNA double helix for both types of binders.

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Dynamical Treatment of Charge Transfer through Duplex Nucleic Acids Containing Modified Adenines

Cited by 8 publications

References 72 publications

Effects of Structural Dynamics on Charge Carrier Transfer in B-DNA: A Combined MD and RT-TDDFT Study

Effects of Structural Dynamics on Charge Carrier Transfer in B-DNA: A Combined MD and RT-TDDFT Study

Probing the Influence of Citrate-Capped Gold Nanoparticles on an Amyloidogenic Protein

Atomistic account of structural and dynamical changes induced by small binders in the double helix of a short DNA

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