Restrained molecular dynamics studies on complex of adriamycin with DNA hexamer sequence d-CGATCG

Jain, Monica ; Barthwal, Sudhir Kumar ; Barthwal, Ritu ; Govil, Girjesh (2005) Restrained molecular dynamics studies on complex of adriamycin with DNA hexamer sequence d-CGATCG Archives of Biochemistry and Biophysics, 439 (1). pp. 12-24. ISSN 0003-9861

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Adriamycin is an anthracycline anticancer drug used widely for solid tumors in spite of its adverse side effects. The solution structure of 2:1 adriamycin-d-(CGATCG)2 complex has been studied by restrained molecular dynamics simulations. The restraint data set consists of several intramolecular and intermolecular nuclear Overhauser enhancement cross-peaks obtained from two-dimensional nuclear magnetic resonance spectroscopy data. The drug is found to intercalate between CG and GC base pairs at two d-CpG sites. The drug-DNA complex is stabilized via specific hydrogen bonding and van der Waal's interactions involving 4OCH3, O5, 6OH, and NH3+ moiety of daunosamine sugar, and rings A protons. The O-glycosidic bond C7-O7-C1'-C2' lies in the range 138°-160° during the course of simulations. The O6-H6...O5 hydrogen bond is stable while O11-H11...O12 hydrogen bond is not favored. The intercalating base pairs are buckled and minor groove is wider in the complex. The phosphate on one strand at intercalation site C1pG2 is in BI conformation and the phosphates directly lying on opposite strand is in BII conformation. The phosphorus on adjacent site G2pA3 is in BII conformation and hence a distinct pattern of BI and BII conformations is induced and stabilized. The role of various functional groups by which the molecular action is mediated has been discussed and correlated to the available biochemical evidence.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Adriamycin-d-(CGATCG) Complex; NMR Restraints; Restrained Molecular Dynamics; Correlation between Structural Parameters; Drug-DNA Interactions; Role of Functional Groups
ID Code:15377
Deposited On:13 Nov 2010 09:10
Last Modified:14 Feb 2011 08:47

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