title: 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.
authors.affiliation: a Department of Chemistry , University of Isfahan , Isfahan , Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Fani
authors.forename: Abdol-Khalegh
authors.initials: AK
authors.lastname: Bordbar
authors.forename: Yousef
authors.initials: Y
authors.lastname: Ghayeb
authors.forename: Saghi
authors.initials: S
authors.lastname: Sepehri
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D054659:Diketopiperazines / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D026121:Indole Alkaloids / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010879:Piperazines / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics; D014404:Tubulin / Q000737:chemistry*; D050257:Tubulin Modulators / Q000737:chemistry*
chemical_list: D054659:Diketopiperazines; D026121:Indole Alkaloids; D010879:Piperazines; D021122:Protein Subunits; D014404:Tubulin; D050257:Tubulin Modulators; C097858:tryprostatin A; D011392:Proline
keywords: Tryprostatin; diketopiperazine; molecular docking; molecular dynamics simulation; αβ-tubulin