Integrating docking and molecular dynamics approaches for a series of proline-based 2,5-diketopiperazines as novel αβ-tubulin inhibitors

Abstract

In this work, docking tools were utilized in order to study the binding properties of more than five hundred of proline-based 2,5-diketopiperazine in the binding site of αβ-tubulin. Results revealed that 20 compounds among them showed lower binding energies in comparison with Tryprostatin-A, a well known tubulin inhibitor and therefore could be potential inhibitors of tubulin. However, the precise evaluation of binding poses represents the similar binding modes for all of these compounds and Tryprostatin-A. Finally, the best docked complex was subjected to a 25 ns molecular dynamics simulation to further validate the proposed binding mode of this compound.

Keywords:

• diketopiperazine
• αβ-tubulin
• molecular docking
• molecular dynamics simulation
• Tryprostatin

Acknowledgments

The financial supports of research council of Isfahan University of Technology, Isfahan University, Abdus Salam International Center for Theoretical Physics (ICTP, Trieste, Italy) and National elites foundation are gratefully acknowledged.