Dynamical Recrossing in the Intercalation Process of the Anticancer Agent Proflavine into DNA
| Autor: | James T. Hynes, Valiamadapally M. Hridya, Arnab Mukherjee |
|---|---|
| Přispěvatelé: | Indian Institute of Science Education and Research Pune (IISER Pune), University of Colorado [Boulder], Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Entropy Intercalation (chemistry) Complex system Antineoplastic Agents [SDV.CAN]Life Sciences [q-bio]/Cancer 010402 general chemistry 01 natural sciences Measure (mathematics) chemistry.chemical_compound Entropy (classical thermodynamics) Transition state theory 0103 physical sciences Materials Chemistry Transmission coefficient Physical and Theoretical Chemistry Proflavine Physics MESH: Proflavine MESH: Kinetics [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] 010304 chemical physics MESH: DNA Energy landscape DNA MESH: Entropy Intercalating Agents 0104 chemical sciences Surfaces Coatings and Films MESH: Intercalating Agents Kinetics chemistry Chemical physics [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Thermodynamics MESH: Antineoplastic Agents MESH: Thermodynamics MESH: Models Molecular |
| Zdroj: | Journal of Physical Chemistry B Journal of Physical Chemistry B, American Chemical Society, 2019, 123 (51), pp.10904-10914. ⟨10.1021/acs.jpcb.9b08470⟩ |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.9b08470 |
| Popis: | International audience; Intercalation into DNA is the interaction mode of some anthracycline antibiotics. Recently, the molecular mechanism of this process was explored using the static free energy landscape. Here we explore the dynamical effects in the intercalation of proflavine into DNA by calculating the transmission coefficient κ-providing a measure of the departure from transition state theory for the reaction rate constant-by examination of the recrossing events at the transition state. For that purpose, we first found the accurate transition state of this complex system-as judged by a committor analysis-using a set of all-atom simulations of total length 6.3 ms. In a subsequent calculation of the transmission coefficient κ in another extensive set of simulations the small value κ = 0.1 was found, indicating a significant departure from TST. Comparison of this result with Grote-Hynes and Kramers theories shows that neither theory is able to capture this complex system's recrossing events; the source of this striking failure is discussed, as are related aspects of the mechanism. This study suggests that, for biomolecular processes similar to this, dynamical effects essential for the process are complex in nature and require novel approaches for their elucidation. |
| Databáze: | OpenAIRE |
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