Docking and quantitative structure-activity relationship studies for sulfonyl hydrazides as inhibitors of cytosolic human branched-chain amino acid aminotransferase.
We have performed the docking of sulfonyl hydrazides complexed with cytosolic branched-chain amino acid aminotransferase (BCATc) to study the orientations and preferred active conformations of these inhibitors. The study was conducted on a selected set of 20 compounds with variation in structure and activity. In addition, the predicted inhibitor concentration (IC(50)) of the sulfonyl hydrazides as BCAT inhibitors were obtained by a quantitative structure-activity relationship (QSAR) method using three-dimensional (3D) vectors. We found that three-dimensional molecule representation of structures based on electron diffraction (3D-MoRSE) scheme contains the most relevant information related to the studied activity. The statistical parameters [cross-validate correlation coefficient (Q(2) = 0.796) and fitted correlation coefficient (R(2) = 0.899)] validated the quality of the 3D-MoRSE predictive model for 16 compounds. Additionally, this model adequately predicted four compounds that were not included in the training set.
Caballero
Julio
J
Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería en Bioinformática, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile. jcaballero@utalca.cl
Vergara-Jaque
Ariela
A
Fernández
Michael
M
Coll
Deysma
D
D020134:Catalytic Domain; D003600:Cytosol / Q000201:enzymology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology*; D016014:Linear Models; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D000637:Transaminases / Q000037:antagonists & inhibitors* / Q000737:chemistry
D004791:Enzyme Inhibitors; D006834:Hydrazines; C029424:hydrazine; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase