Poster Presentation 2014 International Biophysics Congress

DNA aptamers as theranostic tools to detect and regulate apoptosis (#365)

Md Ashrafuzzaman 1 , C.-Y. Tseng , H. Embark 1 , J. Tuszynski
  1. King Saud University, Riyadh, Saudi Arabia
We have applied maximum entropy fragment based approach (EFBA) to design two sets of DNA aptamers to bind to phosphatidylserine (PS) and Bcl 2 protein. PS migration to the cellular exterior region in the apoptotic process is an important biomarker. By designing PS binding aptamers we can detect the induced apoptosis during anticancer treatment. The Bcl 2 protein binding aptamers are designed for promoting apoptosis through inhibiting anti-apoptotic function of Bcl 2 protein in cancer cells. PS binding aptamers may eventually help us to discover an apoptosis detector to check general anticancer drugs’ efficacy. While Bcl 2 protein binding aptamers will help us to develop novel anticancer drugs to regulate apoptosis. Given structures of PS and BCL 2 protein, EFBA utilized seed and grow strategy and maximum entropy principle to design aptamers to bind to targets. Theoretically designed agents have been taken to rigorous agent-target complex binding assay studies using two techniques namely (i) in silico molecular dynamic simulation to address target binding stability and in vitro detection of agents directly in the target structures. Results from both techniques suggest target molecule PS or Bcl 2 protein specific aptamer binding phenomena following a quantitative energetic scenario. Charge based agent-target van der Waals and electrostatic interaction energetics have been detected to be important mechanisms behind target binding of the agents. M.A. acknowledges grant 12-MED2670-02 from National Plan for Science, Technology and Innovation (Saudi Arabia).