闡述蛋白質、DNA或其它生物分子的原子水平的三維結構的技術。這種方法的運用是基于首先使純化的生物分子結晶為有序排列然后用X射線分析結晶體。之所以使用X射線是因為其波長和原子裂解時的波長一樣，所以晶體作為分子衍射光柵衍射X射線，產生一種可以獲取并分析的衍射圖形。然后用計算機重建初始結構。在實際操作中這一衍射圖形被反復地不斷升高的分辨率處理，結晶學家不斷在建立一個模型結構并按該模型計算出的衍射圖形與實際觀察到的比較。每一次重復都使模型結構與實驗結果更加吻合。當這兩者之間的差異可以忽略時，這一衍射圖形便得到求解。最終的模型提供了被研究分子平均時間上的三維原子水平結構。蛋白靶子的X射線結晶體結構可以識別蛋白質的功能袋。當與自然或人工配體混合時，可以作為藥物設計的有用起始點。蛋白質X射線結構的目錄也為蛋白質結構類型、自然狀態下的折疊和域提供了有用信息。有時這被稱為結構基因組學。

A technique that allows the elucidation of the three-dimensional structure of proteins, DNA, or other biomolecules at atomic-level resolution. This is achieved by first crystallizing the purified biomolecule into ordered arrays and then using X-ray diffraction to analyze the crystals. X-rays are used because they have the same wavelength as the atomic separations so the crystal acts as a molecular diffraction grating to diffract a beam of X-rays, producing a diffraction pattern that can be captured and analyzed. A computer is then used to reconstruct the original structure. In practice the diffraction pattern is iteratively solved at ever-increasing “shells” of resolution; the crystallographer alternates between building a model structure (working in “real” space) and comparing the model’s calculated diffraction pattern with the observed diffraction pattern (working in “reciprocal” space). Each round of iteration brings the model structure into better agreement with the experimental data; when the difference between the two is negligible the diffraction pattern is said to be “solved.” The final model provides a time-averaged three-dimensional atomic-resolution structure of the molecule under study. The X-ray crystal structure of a protein target can identify the functional pockets of the protein and, when complexed with a natural or synthetic ligand, can serve as a useful starting point for rational drug design. X-ray structures of catalogs of proteins have also provided useful information on the types of protein structures, folds and domains found in nature; this is sometimes termed structural genomics.