Experimental and Computational Study of the Interaction of Novel Colchicinoids with a Recombinant Human αI/βI-Tubulin Heterodimer

• Published in: Chemical biology & drug design Vol. 82; no. 1; pp. 60 - 70
• Main Authors: Mane, Jonathan Y., Semenchenko, Valentyna, Perez-Pineiro, Rolando, Winter, Philip, Wishart, David, Tuszynski, Jack A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-07-2013
• Subjects: Binding Sites; colchicine; Colchicine - chemistry; Colchicine - metabolism; Dimerization; drug design; fluorescence spectroscopy; Humans; Kinetics; Molecular Docking Simulation; molecular modeling; Protein Binding; Protein Structure, Tertiary; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Spectrometry, Fluorescence; structure-based drug design; Thermodynamics; tubulin; Tubulin - chemistry; Tubulin - genetics; Tubulin - metabolism
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12132

The binding free energies on human tubulin of selected colchicine and thiocolchicine compounds were determined. Two methods were used for the determination of binding free energies: one is based on theoretical prediction simulating the dissociation of the compound from tubulin using a series of molecular dynamics simulations, and the other method involves a series of experiments that measured the affinity of the compound on a synthetically expressed and purified tubulin protein using a spectrofluorometric technique.
The binding free energies on human tubulin of selected colchicine and thiocolchicine compounds were determined. Two methods were used for the determination of binding free energies: one is based on theoretical prediction simulating the dissociation of the compound from tubulin using a series of molecular dynamics simulations, and the other method involves a series of experiments that measured the affinity of the compound on a synthetically expressed and purified tubulin protein using a spectrofluorometric technique.