Kellogg G E, Abraham D J
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond 23298-0540.
J Mol Graph. 1992 Dec;10(4):212-7, 226. doi: 10.1016/0263-7855(92)80070-t.
Three new routines (LOCK, KEY and LOCKSMITH) for the program HINT (hydrophobic interactions) are described and demonstrated. The KEY routine uses receptor structure to model the hydropathic profile of the ideal substrate for the receptor. The LOCK routine uses substrate or drug structure to model the hydropathic character of the receptor. LOCKSMITH is an algorithm designed to highlight the significant hydropathic features from a collection of agents. Ten allosteric modifiers of hemoglobin that have been characterized biologically and with X-ray diffraction to determine their protein binding sites/conformations illustrate the KEY and LOCKSMITH routines: The LOCKSMITH composite map correctly identifies the structural features and conformation of the more active modifiers. In addition, many hydropathic features of the "ideal" drug predicted by the KEY map overlap with actual structural features of the most active hemoglobin allosteric modifiers.
描述并展示了程序HINT（疏水相互作用）的三个新例程（LOCK、KEY和LOCKSMITH）。KEY例程使用受体结构来模拟受体理想底物的亲水性轮廓。LOCK例程使用底物或药物结构来模拟受体的亲水性特征。LOCKSMITH是一种算法，旨在从一组药剂中突出显著的亲水性特征。十种已通过生物学和X射线衍射表征以确定其蛋白质结合位点/构象的血红蛋白变构调节剂说明了KEY和LOCKSMITH例程：LOCKSMITH复合图正确识别了活性更高的调节剂的结构特征和构象。此外，KEY图预测的“理想”药物的许多亲水性特征与活性最高的血红蛋白变构调节剂的实际结构特征重叠。
