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).