Computational modeling and simulation of the Bcl-2 family: paving the way for rational drug design.

Bcl-2 (B-cell lymphoma 2) family proteins have been studied intensively due to their association with cancer and other human diseases. These proteins were originally associated with the regulation of outer mitochondrial membrane integrity and apoptosis. However, there is experimental evidence that suggests that several members of this family play instrumental roles in other cellular pathways including autophagy, endoplasmic reticulum signaling, mitochondrial morphology and synaptic activity among others. Bcl-2 family proteins have been explored using diverse experimental and theoretical methods to obtain structural information that can provide valuable insight for drug development. This review is focused on computational studies related to Bcl-2 family proteins. Different strategies are described and evaluated, such as Molecular Dynamics simulations, docking, and rational drug design with the aim of demonstrating the importance of structural details of either ligands or proteins. The relevance of the knowledge obtained using these tools to drug design is discussed.