Munshi S, Chen Z, Li Y, Olsen D B, Fraley M E, Hungate R W, Kuo L C
Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA.
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):1053-60. doi: 10.1107/s0907444998003588.
The ability to replace an inhibitor bound to the HIV-1 protease in single crystals with other potent inhibitors offers the possibility of investigating a series of protease inhibitors rapidly and conveniently with the use of X-ray crystallography. This approach affords a fast turnaround of structural information for iterative rational drug designs and obviates the need for studying the complex structures by co-crystallization. The replacement approach has been successfully used with single crystals of the HIV-1 protease complexed with a weak inhibitor. The structures of the complexes obtained by the replacement method are similar to those determined by co-crystallization.
在单晶中将与HIV-1蛋白酶结合的一种抑制剂替换为其他强效抑制剂的能力，为利用X射线晶体学快速便捷地研究一系列蛋白酶抑制剂提供了可能。这种方法能够为迭代合理药物设计快速提供结构信息，并且无需通过共结晶来研究复杂结构。这种替换方法已成功应用于与一种弱抑制剂复合的HIV-1蛋白酶的单晶。通过替换法获得的复合物结构与通过共结晶法测定的结构相似。
