Conformers, Properties of the Anticancer Drug Plocabulin, and its Binding Mechanism with p-Glycoprotein: DFT and MD Studies

Conformers, Properties of the Anticancer Drug Plocabulin, and its Binding Mechanism with p-Glycoprotein : DFT and MD Studies

Lü, X. (författare)

Ma, Y. (författare)

Tao, Y. (författare)

Yan, F. (författare)

Wang, C. (författare)

Zhang, M. (författare)

(creator_code:org_t)

CSIRO Publishing, 2021
2021
Engelska.
Ingår i: Australian journal of chemistry (Print). - : CSIRO Publishing. - 0004-9425 .- 1445-0038. ; 74:7, s. 529-539

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Abstract Ämnesord

Stäng

Plocabulin (PM060184) is a promising new anticancer drug as a microtubule inhibitor. The conformational structure and properties of plocabulin have been studied theoretically. The initial structure was screened by the B3LYP/3-21G∗ method, and then 32 unique conformations were further optimised with the B3LYP/6-311G∗ method. The single-point energies were determined at the M06-L/6-311G(2df,p) level. The UV excitation of the most stable plocabulin conformation in methanol was studied by the TD-CAM-B3LYP/6-311G(2df,p) method. High-quality human p-glycoprotein model was obtained through homology modelling. The binding interaction between p-glycoprotein and plocabulin was studied by docking and MD simulation. LEU65, TYR310, ILE340, THR945, PHE983, MET986, and GLN990 were found to be important amino acid residues in the interaction. From a certain perspective, the 'reverse exclusion' mechanism of plocabulin with p-glycoprotein was illustrated, and this mechanism provides theoretical guidance for the structural modification of plocabulin and for design of drug's to avoid p-glycoprotein-mediated drug resistance.

NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Av författaren/redakt...: Lü, X.; Ma, Y.; Tao, Y.; Yan, F.; Song, Ce; Wang, C.; visa fler...; Zhang, M.; visa färre...

Om ämnet

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