Title:Computational Modeling and Simulation of the Bcl-2 Family: Paving the Way for Rational Drug Design
VOLUME: 19 ISSUE: 36
Author(s):J. L. Rosas-Trigueros, I. Ilizaliturri-Flores, C. G. Benitez-Cardoza, J. Correa-Basurto and A. Zamorano-Carrillo
Affiliation:SEPI-ENMH, Instituto Politecnico Nacional, Guillermo Massieu Helguera No. 239 Fracc. "La Escalera", Ticoman, Mexico City, Mexico C.P. 07320.
Keywords:Apoptosis, Bcl-2, bioinformatics, cancer, molecular modeling, protein–protein interaction, structure-based drug design
Abstract: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.
