Bcl-2 and Bcl-x_L proteins are main members of Bcl-2 protein family, which are new targets of anticancer drugs with bright prospect. These two proteins have similar structure and functions, while differ in many aspects, such as the tumor spectra with high expression of these two proteins, binding selection with other proapoptosis subfamily members, and cell protection function under various apoptosis stimulations. By sequence aligning, structure and surface electrostatic potential comparing of the active sites in Bcl-2 and Bcl-x_L proteins, the dominant differences between them are identified. Then the effect of these differences on substrates binding selection is showed by studies of some substrates for example. The result of this paper provides good basis for understanding molecular mechanism of the function difference between Bcl-2 and Bcl-x_L proteins, and design, synthesis of small molecule inhibitors with good selection.

Key words: Bcl-2 protein family, sequence alignment, structure comparison, surface electrostatic potential, molecular docking