Analysis of Delta–Notch interaction by molecular modeling and molecular dynamic simulation studies

Abstract

Notch is a single-pass transmembrane receptor protein. Delta (member of the DSL protein family), a Notch ligand, is also single-pass transmembrane protein that can interact with Notch to form the Delta–Notch complex. It has been demonstrated that of the 36 Epidermal Growth Factor (EGF) repeats of Notch, 11th and 12th are sufficient to mediate interactions with Delta. Crystal structure of mammalian Notch1 extracellular ligand binding domain shows the presence of 11th and 12th EGF-like repeats. Here a portion of the Drosophila Delta protein, known to interact with Notch extracellular domain, has been modeled using homology modeling. The structure of the Delta–Notch complex was subsequently modeled by protein-docking method using GRAMM. Molecular dynamic simulations of the modeled structures were performed. The probable structures for Delta–Notch complex have been proposed based on interaction energy parameter and planarity studies.

Keywords:

• Delta
• Notch
• Drosophila
• protein–protein docking
• homology modeling
• MD simulation

Acknowledgments

The authors are grateful to the School of Mobile Computing, Jadavpur University, Kolkata for providing access to their AIX server. Basic computational studies were done using the HP server at West Bengal State University, Barasat, Kolkata. RM wants to acknowledge the fellowship from Department of Biotechnology, India. We would also like to acknowledge the help received from the editorial board of JBSD in making this manuscript more complete.

Notes

Authors contributed equally to this work.