Gehlhaar D K, Moerder K E, Zichi D, Sherman C J, Ogden R C, Freer S T
Agouron Pharmaceuticals, Inc., San Diego, California 92121.
J Med Chem. 1995 Feb 3;38(3):466-72. doi: 10.1021/jm00003a010.
A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease. One such improvement resulted in a compound selected for preclinical studies as an antiviral agent against AIDS.
描述了一种用于在蛋白质结合位点原位生成小分子的新计算方法。该方法已通过两个经过充分研究的系统进行评估，即二氢叶酸还原酶和胸苷酸合成酶。该方法还被用于指导对HIV-1蛋白酶抑制剂的改进。其中一项改进产生了一种被选用于临床前研究作为抗艾滋病抗病毒药物的化合物。
