In this work, molecular dynamics simulation and free energy calculations are utilized to study how different BH3 peptides originating from Bax, Bim, Bik and Noxa interact with Bcl-2, one of the main members of anti-apoptotic proteins. The effects of peptide length, sequence and helical content on the binding affinity are discussed, on which a novel BH3-like peptide is designed in silico with an improved binding property. (C) 2017 Elsevier B.V. All rights reserved.