目的 開發(fā)膽固醇酯轉(zhuǎn)移蛋白（CETP）的天然產(chǎn)物抑制劑。方法 采用計算機輔助技術(shù)，對高通量篩選天然產(chǎn)物數(shù)據(jù)庫L6000分別進行3個精度梯度的分子對接、結(jié)合自由能計算、分子動力學模擬（MD模擬）等多輪虛擬篩選的策略，從中篩選CETP抑制劑。結(jié)果 共篩選得到19個候選化合物，其中前3位化合物分別為肉蓯蓉苷A、茶黃素、丹酚酸B二甲酯，結(jié)合模式分析顯示上述化合物與靶標活性口袋之間形成了較強的相互作用；MD模擬的參數(shù)也證實上述蛋白–配體復合物結(jié)合的穩(wěn)定性。結(jié)論 肉蓯蓉苷A、茶黃素、丹酚酸B二甲酯可作為CETP抑制劑的先導化合物。

Objective To develop natural product inhibitors of cholesterol ester transfer protein (CETP). Methods By using computer-aided technology, the high-throughput natural product database L6000 was screened for CETP inhibitors by multi-round virtual screening strategies such as molecular docking with three precision gradients, combined free energy calculation and molecular dynamics simulation (MD simulation). Results A total of 19 candidate compounds were screened, of which the first three compounds were cistanosideA, theaflavin and dimethyllithospermate B. Binding mode analysis showed that there was a strong interaction between the above compounds and the active pocket of the target, and the MD simulation parameters also confirmed the stability of the protein-ligand complex mentioned above. Conclution CistanosideA, theaflavin, and dimethyllithospermate B can be used as the lead compounds of possible CETP inhibitors.

R972

國家自然科學基金資助項目（81873060）