Virtual and experimental screening of protease activated receptor 1 antagonist in plant ingredients / 中草药

ABSTRACT

Objective: To find the new type of structures with protease activated receptor 1 (PAR-1) inhibition from plant ingredients. Methods: Thirty ingredients were docked into PAR-1, and then, docking score, occupied space, hydrogen bonding, and other indicators were used for virtual screening. In vitro platelet aggregation experiments in guinea pig were performed to screen the activities of all ingredients. Results: Virtual screening suggested that T30 and T21 had the prospects to inhibit PAR-1. Experiment screening showed that T21, T5, T28, and T29 have the real inhibitory effects on PAR-1. Combination analyses of virtual and experimental screening suggested the following results. Residue 258 and area III had the key effects. Hydrogen matching was required at area II. Area IV and V regions mainly need hydrophobic match. The hydrogen bonding played an important role in improving the activity. Conclusion: According to the binding mode of control drug, T21 is found. To examine the binding mode of T5, T28, and T29, their experimental activities suggest a novel action mode which provides a new direction to find the PAR-1 antagonist.