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Molecular dynamics simulation of the sliding of distamycin anticancer drug along DNA: interactions and sequence selectivity

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Abstract

Molecular dynamics simulations and umbrella sampling have been used to investigate the sliding of distamycin anticancer drug along the DNA minor groove. The potential energy surface calculated for the sliding of drug shows three minima. The global minimum corresponds to the binding of drug to the AT-rich region, which is the origin of sequence selectivity of distamycin. This selectivity originates from both structural factors and energy contributions. The analysis of energy contributions of binding was performed by the MM–PBSA method. The analysis of hydrogen bonds and van der Waals, electrostatic, and solvation interactions show that structural or steric factors are more important in the selectivity of distamycin than energetic factors. The results of this study can be applied in the design of new derivatives of distamycin anticancer drug with improved properties.

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Authors and Affiliations

  1. Department of Chemistry, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran

    Seifollah Jalili & Mina Maddah

  2. Computational Physical Sciences Research Laboratory, School of Nano-Science, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran, Iran

    Seifollah Jalili

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  1. Seifollah Jalili
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Correspondence to Seifollah Jalili.

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Jalili, S., Maddah, M. Molecular dynamics simulation of the sliding of distamycin anticancer drug along DNA: interactions and sequence selectivity. J IRAN CHEM SOC 14, 531–540 (2017). https://doi.org/10.1007/s13738-016-1001-0

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