VEGFR2, which plays crucial roles in angiogenesis induced by tumor, is a new ideal target for inhibiting development and metastasis of tumor. To study the properties of VEGFR2 active site and binding mode of VEGFR2 and its inhibitors, MCSS (Multiple Copy Simultaneous Search) method was applied to explore properties of active site of VEGFR2. Then five inhibitors which are under clinical trial evaluations were docked into the active site of VEGFR2 to study the mode of interaction and to determine the critical residues involved in binding. It was found that hydrophobic pockets I and II are crucial for inhibitors’ binding. Glu915 and Cys917 residues are crucial hydrogen bond acceptor and donor respectively. A polar zone formed by Lys866, Glu883 and Asp1044 is important for ligands’ binding. Hydrophobic pocket III and polar pocket IV enhance binding affinity additionally. Arg1030 residue serves as an additional hydrogen bond donor. These results provide a basis for rational design of novel potent VEGFR2 inhibitors and for discovery of new anticancer drugs.

Key words: multiple copy simultaneous search, molecular docking, VEGFR inhibitor