根据受体三维结构搜鼠配体活性构象的方法及在凝血酶抑制剂.PDF

36 ． BIBLID．ISSN0253．9756 ActaPharmaco]ogicaSin[ca 中国药理学报 1997Jan；18( 甘肤氧化酶 、还原酶和转移酶类均无 明显作用． 化氢酶．Hed还增加肝脏抗坏血酸含量2O％，但 Hed诱导肝金属藏蛋 白50倍 ，并 同时增加肝脏锌 对维生素E含量无明显影响． 结论：Hed的保肝 (8O％)和铜 (30％)含量．Hed对超氧化物歧化 作用至少在某一方面是 由于诱导肝脏非酶类的抗 酶，蒽酮还原酶无明显影 响，太剂量时降低过氧 氧化损伤物质 ． B1BLID．ISSN0253．9756 诅Pharmaeolo$icaSinica 中国药理学报 1997Jaa；18(1)：36—44 Bindingconformerssearchingmethod forligandsaccordingtothestructuresof theirreceptorsanditsapplicationtothrombin inhibitors JIANGHua—Liang，CHEN Kai-Xian，TANGYun，CHEN Jian—Zhong，LIQuan，WAN GQin-Mi， JIRu．Yun (ShanghaiInstituteofMateriaMedica，ChineseAcademyofSciences，hSanghai200031，hCina) KEY WORDS molecular conformation；phos— interaction fashions，onecan design novelligands phonopeptides thrombin rceepotr； lJganad which might bind to the receptors tightly ． strueotre-activityrelatiom~fip molecularm~benlcs Nowadays， there is accumulating evidence that ligand—receptor non—covalent interactions can be AIM ：To develop a method offinding binding modeled and simulated with relatively simple conformers for ligands according to the three- molecu1armechanicalapproaches[ Amongthese dimensional struettu~s of hteir receptors． approaches，thekey difference，ofCOUles ，isthe METHODS： Combining the systematic search sampling problme ，sinceone should，in principle， method of and wiht hte molecular docking considerthemanyalternativeconformationalstates approach of ligand fitting inot itsrceeptro ，we of the macmmolceule， the 1igna ds， and the devdopedabinding c0nf锄 口 searching methodfro complexes of them [． But how to recognize liganad ． RESULTS：Thebinding con~ylnle2sof binding (bioactive)conformerofalignadwhen phosphonopeptidyl thrombin inhibiotrs were