In silico investigation of potential pyruvate kinase M2 regulators from traditional Chinese medicine against cancers.

Abstract	A recent research in cancer research demonstrates that tumor-specific pyruvate kinase M2 (PKM2) plays an important role in chromosome segregation and mitosis progression of tumor cells. To improve the drug development of TCM compounds, we aim to identify potent TCM compounds as lead compounds of PKM2 regulators. PONDR-Fit protocol was utilized to predict the disordered disposition in the binding domain of PKM2 protein before virtual screening as the disordered structure in the protein may cause the side effect and downregulation of the possibility of ligand to bind with target protein. MD simulation was performed to validate the stability of interactions between PKM2 proteins and each ligand after virtual screening. The top TCM compounds, saussureamine C and precatorine, extracted from Lycium chinense Mill. and Abrus precatorius L., respectively, have higher binding affinities with target protein in docking simulation than control. They have stable H-bonds with residues A:Lys311 and some other residues in both chains of PKM2 protein. Hence, we propose the TCM compounds, saussureamine C and precatorine, as potential candidates as lead compounds for further study in drug development process with the PKM2 protein against cancer.
Authors	Kuan-Chung Chen, Kuen-Bao Chen, Hsin-Yi Chen, Calvin Yu-Chian Chen
Journal	BioMed research international (Biomed Res Int) Vol. 2014 Pg. 189495 ( 2014) ISSN: 2314-6141 [Electronic] United States
PMID	25089263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins Ligands Membrane Proteins Thyroid Hormones saussureamine C thyroid hormone-binding proteins precatorine Asparagine Tryptophan Lysine
Topics	Asparagine (analogs & derivatives, chemistry) Binding Sites Carrier Proteins (chemistry) Chemistry, Pharmaceutical (methods) Computational Biology Crystallography, X-Ray Drug Design Humans Hydrogen Bonding Ligands Lysine (chemistry) Medicine, Chinese Traditional Membrane Proteins (chemistry) Mitosis Molecular Dynamics Simulation Neoplasms (drug therapy) Protein Conformation Thyroid Hormones (chemistry) Tryptophan (analogs & derivatives, chemistry)

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