Bcl-2 protein is a new target of anticancer drugs with bright prospect now. The active site of Bcl-2 protein is a protein-protein interface under physiological condition, and involves large and relatively flat surface areas and obvious induced fit when binding substrates. By analyzing and comparing nine correlative 3D structure models of Bcl-2 and homological Bcl-x_L protein in free or complex state, the backbone structure features, key sites and induced fit of proteins and their active sites were identified. Based on above knowledge, a reasonable binding mode of a highly potent inhibitor to Bcl-2 has been developed using flexible docking techniques, which provides good basis for further design and synthesis of novel potent Bcl-2 protein inhibitors.

Key words: Bcl-2 protein, structure comparison, induced fit, molecular docking, anticancer drug