Methods and compositions for rendering nucleic acids directly responsive to an external signal utilizing modulators that themselves respond to the external signal and are associated with the nucleic acid. In response to the external signal, the modulator alters physical properties of the specific nucleic acid molecule(s) with which it is associated, thereby altering the structural and functional properties thereof. The modulator may, for example, transfer applied energy to a nucleic acid, or to a portion of the nucleic acid, thereby changing the nucleic acid structure.