在综合系统构象搜寻和配体-生物大分子对接(Dock)方法的基础上,发展了根据受体活性部位三维结构搜寻配体活性构象的搜寻方法BCSPL.用此方法搜寻了凝血酶抑制剂PPACK的活性构象,结果与晶体结构非常吻合,又用此方法搜寻了膦酰肽类和二肽、三肽类凝血酶抑制剂与人体α凝血酶结合时的活性构象,并在此基础上用分子力学计算了抑制剂与凝血酶的结合能,结果表明结合能与活性有很好的相关性,计算结果能合理地解释抑制剂与凝血酶的相互作用方式及结构与活性的关系. Based on the systematic conformation search and Dock-method, BCSPL, a search method to search for the active conformation of ligands based on the three-dimensional structure of the active site of the receptor, has been developed. The thrombin inhibitor PPACK Activity conformation, the result is very consistent with the crystal structure, but also using this method to search for phosphopeptides and dipeptides, tripeptide thrombin inhibitors and human α-thrombin when the active conformation, and on this basis with molecules The binding energies of inhibitors and thrombin were calculated by mechanics. The results showed that there was a good correlation between the binding energy and the activity. The calculated results can reasonably explain the mode of the interaction between the inhibitor and thrombin and the relationship between structure and activity.