Dynamical binding of hydrogen-bond surrogate derived Bak helices to antiapoptotic protein Bcl-xL.

ABSTRACT: A new peptide modification strategy was recently developed to replace the i to i + 4 hydrogen bond of the main chain of an alpha-helix with a carbon-carbon covalent bond to afford highly stable constrained alpha-helices, termed hydrogen-bond surrogate (HBS) helices. HBS helices that mimic the Bak BH3 domains were experimentally demonstrated to target protein Bcl-x(L) with high affinity. In this study, molecular dynamics (MD) simulation is used to understand how the covalent modification of the natural Bak sequence affects the binding to Bcl-x(L) at molecular levels. The binding mechanism of HBS helix to Bcl-x(L) and the effect of synthesized cyclic structures are analyzed by MD and MM-PBSA calculations for comparison with the native binding of Bak-Bcl-x(L). The present MD result shows that

SUBMITTER: Bao J 

PROVIDER: S-EPMC4578800 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature