S-1360引起HIV-1整合酶多位点耐药突变的机理

Mechanism Study on Drug Resistance of HIV-1 Integrase Caused by S-1360

摘要: 为了探讨二酮酸类药物引起整合酶的耐药性机制,选取S-1360存在下产生的HIV耐药突变株TEQ:T661,E138K,Q146K和TLAEQSKVV:T66I,L74M,A128T,E138K,Q146K,S153A,K160D,V1651,V2011进行了分子动力学等计算机模拟研究.结果表明,S-1360引起IN产生耐药性与Loop区及Loop2区的柔性有关,并且耐药突变导致Helix4和Loop区相连处的结构发生变化.

Abstract: In order to explore the drug-resistance mechanism of IN,two drug-resistance mutant caused by Diketo Acid HIV integrase inhibitors:TEQT66I,E138K,Q146Kand TLAEQSKVVT66I,L74M, A128T,E138K,Q146K,S153A,K160D,V165I,V201Iwere chosen to perform molecule dynamics study. The results show that the flexibilities changing of Loop and Loop2 regions and the structure changing between Helix4 and Loop region are relevant to drug-resistance.