DNA aptamers previously selected as calcium phosphate mineralization templates were modified and analyzed to better understand structure−function relationships and to explore the mechanism of templated mineralization. Aptamers were created to strengthen or remove a prevalent G-quadruplex structure and were analyzed for structural stability, affinity to calcium phosphate, influence on homogeneous and heterogeneous calcium phosphate mineralization, and influence on mineral crystallinity and morphology. Aptamers were found to modulate mineralization kinetics in a concentration-dependent manner. Changes to the G-quadruplex structure affected affinity to hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , HAP) and had a substantial impact on the mineral crystallinity. We propose a model for aptamer-directed mineralization and anticipate the usefulness of these aptamer sequences in future biomimetic and biomedical applications.