HIV蛋白酶多肽抑制剂的理论研究

艾滋病病毒的发现距今已有二十多年的历史了.它仍然以很快的速度在全球范围速蔓延.研发抗艾滋病药物是当代药学的重大课题之一.在以往研究的基础上,我们利用分子叠合和分子对接这两种分子模拟手段,把从PDB数据库中得到的与HIV蛋白酶结合的12个肽类分子和已经上市的抗艾滋病的药物Saquinavir做比较.根据结构相同或相近的分子具有相同的活性原理,运用分子叠合初部判断分子活性,特别是药效团的特征比对揭示了分子活性的原因,为进一步的药物设计奠定了良好的基础.进而采用分子对接的分子模拟方法对这12个肽类分子的活性构象进行了深入的分析,预测出了这12个分子对HIV病毒蛋白酶的不同抑制作用.研究发现:P01、P05、P09、P12可能与已知药物Saquinavir在与HIV蛋白酶结合时具有相似的活性,其中P9的活性最强,有望成为抗HIV药物的理想前体,为下一步的HIV药物的设计研究提供了理论依据.

Modeling studies of peptide inhibitors for the HIV protease

It has been twenty years since the first discovery of the HIV virus.HIV remains to be a major throat to human health all over the world.Based on the experimental works and crystal structure of the HIV ligand binding protease,we investigated 12 peptides in complex with the HIV protease found in the PDB bank,using flexible molecule alignment and molecular docking.The alignment gives clues which molecule could have good binding potential.By comparing the distribution of pharmacophore points and comparing against with those of Saquinavir we could elucidate molecular basis for binding.Further studies are made with molecular docking.We find that P1,P5,P9,P12 have good binding with the protease,among them P9 is the best one.Further studies with its drugbility as an HIV protease inhibitor are under way.