Molecular dynamics simulation of the inhibition mechanism of factor XIa by Milvexian-like macrocyclic inhibitors

•1. Factor XIa inhibitors have become a hot topic for their ability to block thrombosis without increasing the risk of bleeding.•2. Molecular dynamics simulations and MM-PBSA were used to study the inhibition mechanisms of five macrocyclic inhibitors.•3. The reasons for the different inhibitory abilities of the inhibitors with different substituents in the nucleus were summarized.•4. The present work has implications for the design of more efficient anticoagulant drugs for FXIa macrocyclic inhibitors.