DesJarlais R L, Sheridan R P, Dixon J S, Kuntz I D, Venkataraghavan R
J Med Chem. 1986 Nov;29(11):2149-53. doi: 10.1021/jm00161a004.
We present a method to explore the interaction of flexible ligands with receptors of known geometry on the basis of molecular shape. This method is an extension of that described by Kuntz et al. (J. Mol. Biol. 1982, 161, 269). The shape of a binding site on a macromolecular receptor is represented as a set of overlapping spheres. Each ligand is divided into a small set of large rigid fragments that are docked separately into the binding site and then rejoined later in the calculation. The division of ligands into separate fragments allows a degree of flexibility at the position that joins them. The rejoined fragments are then energy minimized in the receptor site. We illustrate the method with two test cases: dihydrofolate reductase/methotrexate and prealbumin/thyroxine. For each test case, the method finds binding geometries for the ligand near that observed crystallographically as well as others that provide good steric fit with the receptor.
我们提出了一种基于分子形状来探索柔性配体与已知几何形状受体之间相互作用的方法。该方法是对Kuntz等人（《分子生物学杂志》，1982年，第161卷，第269页）所描述方法的扩展。大分子受体上结合位点的形状表示为一组重叠球体。每个配体被分成一小组大的刚性片段，这些片段分别对接至结合位点，然后在计算后期重新连接。将配体分成单独的片段可在连接它们的位置实现一定程度的灵活性。然后在受体位点对重新连接的片段进行能量最小化处理。我们用两个测试案例来说明该方法：二氢叶酸还原酶/甲氨蝶呤和前白蛋白/甲状腺素。对于每个测试案例，该方法都能找到配体在晶体学观察到的结合几何结构附近的结合几何结构，以及与受体具有良好空间契合度的其他结合几何结构。
