How Do Mutations and Allosteric Inhibitors Modulate Caspase-7 Activity? A Molecular Dynamics Study

Bingol E. N. , Serçinoğlu O., Özbek Sarıca P.

Journal Of Biomolecular Structure & Dynamics, vol.37, no.13, pp.3456-3466, 2019 (Journal Indexed in SCI) identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 13
  • Publication Date: 2019
  • Doi Number: 10.1080/07391102.2018.1517611
  • Title of Journal : Journal Of Biomolecular Structure & Dynamics
  • Page Numbers: pp.3456-3466


Caspases are members of a highly regulated aspartate-cysteine protease family which have important roles in apoptosis. Pharmaceutical studies focused on these molecules since they are involved in diseases such as cancer and neurodegenerative disorders. A small molecule which binds to the dimeric interface away from the binding site induces a conformational change that resembles the pro-caspase form of the molecule by shifting loop positions. The fluctuation mechanisms caused by mutations or binding of a ligand can explain the key mechanism for the function of that molecule. In this study, we performed molecular dynamics simulations on wild-type and mutated structures (C290N, R187M, Y223A, G188L and G188P) as well as allosterically inhibited structure (DICA-bound caspase-7) to observe the effects of the single mutations on intrinsic dynamics. The results show that previously known changes in …