caa a22 4500 605512663 CHVBK 20210128100656.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00894-015-2627-z doi (NATIONALLICENCE)springer-10.1007/s00894-015-2627-z Molecular dynamics study of the inhibitory effects of ChEMBL474807 on the enzymes GSK-3β and CDK-2 [Elektronische Daten] [Przemysław Czeleń, Beata Szefler] Indirubin derivatives and analogs comprise a significant group of ATP-competitive inhibitors. The inhibitory effects of ChEMBL474807 (1-(4-amino-1,2,5-oxadiazol-3-yl)-5-(piperidin-1-ylmethyl)-N′-(pyridin-4-ylmethylene)-1H-1,2,3-triazole-4-carbohydrazide) on two enzymes, namely glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-2 (CDK-2), were analyzed. The close resemblance of the amino acid sequences of these two enzymes (with 25% identity and 41% similarity) explains why indirubin derivatives are inhibitors of both of the enzymes studied. The docking and molecular dynamics investigation performed here led to the identification of the interactions responsible for stabilizing the ligand ChEMBL474807 at the active sites of the enzymes considered. The structural and energetic data collected during our investigations clearly indicate that there are important differences in the behavior of the ligand at the two active sites investigated here. The Author(s), 2015 ATPase nationallicence Competitive inhibition nationallicence Similarity nationallicence Molecular dynamics nationallicence CDK-2 nationallicence GSK-3β nationallicence Czeleń Przemysław Department of Physical Chemistry, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-950, Bydgoszcz, Poland aut Szefler Beata Department of Physical Chemistry, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-950, Bydgoszcz, Poland aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-8 1610-2940 21:4<1 2015 21 894 https://doi.org/10.1007/s00894-015-2627-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2627-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Czeleń Przemysław Department of Physical Chemistry, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-950, Bydgoszcz, Poland aut NATIONALLICENCE 700 1- Szefler Beata Department of Physical Chemistry, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-950, Bydgoszcz, Poland aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-8 1610-2940 21:4<1 2015 21 894