关键词: HIV-1蛋白酶抑制剂, 利迪链菌素, 分子模拟, 分子对接

The HIV protease-inhibiting activity of streptolydigin was studied using docking methodology. To reflect the binding state of streptolydigin and enzyme receptor more exactly, the flexibility of the active site was taken into consideration. A two-step docking method involving FlexX (for rough docking) and Flexidock (for precise docking) was used. In rough docking, in order to find out whether there is a structural water molecule mediating the contacts of the ligands and the protease, two different active site models were designed. The two-step docking result was obtained for Aha006, a non-peptide HIV-1 protease inhibitor whose binding mode in the active site is already known. The docking result coincided with actual binding state of ligand and receptor, indicating that the docking method used was reliable. The binding result of streptolydigin and active site of HIV-1 protease exhibited that the ligand binds to the active site under the help of five hydrogen bonds and no water molecule participates in the binding. Streptolydigin molecule oc-cupies the binding site and covers the active-site triad (Asp25-Thr26-Gly27), thus the biological activity of the protease is inhibited.

Key words: HIV-1 protease inhibitor, streptolydigin, molecular modeling, docking