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.
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