Input-dependent induction of oligonucleotide structural motifs for performing molecular logic

Area of Science:

• Biochemistry and Molecular Biology
• Supramolecular Chemistry
• Nanotechnology

Background:

• Nucleic acids exhibit diverse structural forms beyond canonical duplexes, including G-quadruplexes and i-motifs.
• These structures are sensitive to ions (e.g., K+) and pH, leading to conformational changes.
• Such stimuli-responsive structural transitions offer potential for molecular information processing.

Purpose of the Study:

• To investigate the K(+)- and H(+)-triggered structural conversions of various nucleic acid helices.
• To explore the application of these structural interconversions in performing molecular logic operations.
• To establish a signaling mechanism for detecting these molecular events using G-quadruplex/hemin complexes.

Main Methods:

• Gel electrophoresis, circular dichroism, and thermal denaturation were used to study structural conversions.
• Fluorimetry and colorimetry were employed to verify molecular logic operations.
• Hybridization of G-rich and C-rich strands, followed by K+ and pH stimuli, and G-quadruplex/hemin complex formation for signal detection.

Main Results:

• K+ addition induced unwinding of duplexes and folding of G-rich strands into G-quadruplexes.
• Decreased pH led to i-motif formation in DNA or triplex formation in RNA, depending on strand composition.
• G-quadruplex/hemin complexes catalyzed reactions producing fluorescence or colorimetric signals, enabling logic gate operations (NOR, INH, AND).

Conclusions:

• Nucleic acid structural interconversions driven by K+ and pH can be harnessed for molecular computation.
• The G-quadruplex/hemin system provides a versatile platform for signal transduction in molecular logic gates.
• This study demonstrates a framework for developing responsive nucleic acid-based molecular devices.