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Articles

Vol. 1 No. 3 (2010): July–September 2010

The Binding of Acridine-4- Carboxamides within DNA Sequences: An Ab-initio and Force Field Studies

  • Bipul Bezbaruah
  • Pankaj Hazarika
  • Chitrani Medhi
Submitted
November 24, 2024
Published
2010-08-15

Abstract

The sequence specific chromophore intercalation as well as side chain binding of acridine-4-carboxamide(AC) within various sequences of DNA oligomer have been investigated by using Force Field and ab initio calculations. The intercalation of chromophore within various sequence combinations such as d(ApCpGpT)(SEQ1), d(TpCpGpG)(SEQ2) and d(GpTpCpG)(SEQ3) sequences are found different. The results provide useful information on the sequence selectivity of chromophore intercalation in DNA binding. The side chain binding within d(ApCpGpT)(SEQ1) is also evidenced, herein a distinct hydrogen bond between thymine and nitrogen atom of carboxamide side chain is found in the minimized structure of AC-SEQ1 complex. The computed interaction energies obtained from HF/6-31G calculations for the minimized structures of AC-SEQ1 and AC-SEQ2 are found positive whereas negative values are obtained for AC-SEQ3. The interaction energies for 5'3' orientation of side chain are -18.80 and -1.11 kcal/mol and the values for 3'5' orientation are -4.95 kcal/mol and -3.40 kcal/mol. Distinct hydrogen bond formed between side chain and thymine nucleobase in AC-SEQ3 for the 5'3' orientation within major groove of DNA results large negative interaction energy (-18.80 kcal/mol). So the chromophore intercalation may not be the major factor for the sequence selective binding of drug within oligomer, however the side chain selectivity might be important if thymine nucleobase is present within certain regions of DNA to form hydrogen bond.

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