The selection of a protein structure is an important step for the success of the drug discovery process using structure-based design. Selection of the right crystal structure is critical as multiple crystal structures are available for the same protein in the Protein Data Bank (PDB). In this communication, we have discussed a systematic approach for selecting the right type of protein structure. Selecting crystal structures of TACE, 11β-HSD1, DprE1, and SARS-CoV-2 M enzymes for some case studies have been discussed for illustration.