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. Method: 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 Conclusion: 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.Keywords: Beta lactamase, binding energy, indolizines, molecular docking, molecular dynamics, nicotinamide phosphoribosyltransferases.
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