Bioinspired metal-organic frameworks (MOFs) serve as suitable crystalline models for recognition and sensing of biomolecules mimicking natural processes, providing new ideas and concepts for cutting-edge biomedical applications. Here, we have successfully prepared a robust biological metal-organic framework with periodic docking grooves resembling the major and minor grooves in the DNA double helix structure, which can be used as unique recognition sites for selectively identifying l-/d-tryptophan (l-/d-Trp). Notably, successful encapsulation of Trp could be observed by single-crystal X-ray diffraction for the first time. Trp has matched size and shape to fit snugly into the major groove. Combined with isothermal titration calorimetry, it was found that ZnBTCHx could spontaneously capture l-/d-Trp through two different thermodynamic pathways: enthalpy-driven for encapsulating l-Trp and entropy-driven for uptaking d-Trp. Furthermore, molecular dynamics and density functional theory verified the role of hydrogen bonding and π-π/C-H···π interactions in the host-guest interface. This work provides unique insight for the construction of bionic models to mimic the natural binding properties, which is of great significance for the fields of pharmaceutical chemistry and biomedical science.