title: Understanding the Action of Indolizines as Biologically Active Moieties: A Molecular Dynamics Study.
abstract: BACKGROUND
  Indolizines represent a class of heteroaromatic compounds, of pharmacological importance, containing two condensed 5- and 6-memebered rings bridged by a nitrogen atom. Despite indolizine is an important medicinal moiety, a detailed view on the mechanism of action of biologically active indolizines is unavailable.
  
  
  OBJECTIVE
  The study of ligand-enzyme affinity is of high interest; description of characteristics (energetic and geometric ones) of ligand binding to the active sites of an enzyme could be useful in understanding the action mechanism of a given ligand on the concerned enzyme.
  
  
  METHODS
  After conducting a QSAR study, to predict IC50 (on 15-LO protein from soybeans) of indolizine derivatives and a docking study of indolizines on Beta lactamase and Nicotinamide phosphoribosyltransferase proteins [1], a molecular dynamics analysis was performed on one of the indolizine derivatives, complexed to the above proteins.
  
  
  RESULTS
  The performed molecular dynamics study led to the identification of interactions responsible for the stabilization of complexes of the chosen ligand (i.e., indolizine derivative) with the considered enzymes and the specificity of the ligand interaction as well. The structural data and enthalpy values clearly indicate the differences in the behavior of ligand at the active sites of the three investigated enzymes. Among the studied proteins, the hydrophobicity of the active site of Nicotinamide phosphoribosyltransferase seems to be the main factor in promoting the interaction enzyme-ligand, much more manifested in this case, in comparison to the other two proteins Beta lactamase and Nicotinamide phosphoribosyltransferase.
  
  
  CONCLUSIONS
  The present paper discusses a possible mechanism of interaction of an indolizine derivative with three enzyme proteins, providing information for future work in this topic.
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpi.skiego 5, 85-096, Bydgoszcz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Szefler
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Czelen
authors.forename: Mircea V
authors.initials: MV
authors.lastname: Diudea
mesh_terms: D020134:Catalytic Domain / Q000187:drug effects*; D007212:Indolizines / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D054409:Nicotinamide Phosphoribosyltransferase / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D007212:Indolizines; D054409:Nicotinamide Phosphoribosyltransferase; D001618:beta-Lactamases
keywords: Beta lactamase; binding energy; indolizines; molecular docking; molecular dynamics; nicotinamide phosphoribosyltransferases.