Interaction study of Dox-incorporated AS1411 aptamer and nucleolin by molecular dynamics simulation

Abstract

ABSTRACT AS1411 aptamer is able to recognise the nucleolin overexpressed on cancer cell membranes and has shown promise as a carrier of doxorubicin (Dox) to the cells. This study aimed to study the interaction between nucleolin and aptamers, in either the absence or presence of Dox, using molecular dynamics simulation. AS22nt aptamer was constructed by joining AS1411 aptamer with an additional 22 nucleotide (nt) sequence. NPT simulations were performed from initial docked configuration predicted by HDOCK. The binding of Dox to AS22nt aptamer occurred at the minor groove and the intercalation site in the duplex region. Nucleolin exhibited less flexibility upon binding to AS22nt. The dominant interaction between nucleolin and AS22nt was the electrostatic interaction. The presence of Dox in AS22nt affected the AS22nt-nucleolin interaction contributed by hydrogen bond, hydrophobic contact and ionic interaction. However, the presence of Dox in AS22nt had no impact on the interaction between nucleolin and AS22nt because the magnitudes of binding energy of nucleolin and aptamer with Dox or without Dox were comparable and they were within their calculated deviation. This understanding of nucleolin, AS1411 aptamer, and Dox interactions could provide us a way to prepare an effective targeted anticancer agent for cancer-suffering patients.