Imatinib (Gleevec@) conformations observed in single crystals, protein–Imatinib co-crystals and molecular dynamics: Implications for drug selectivity

Structure and dynamics of the Leukemia drug, Imatinib, were examined using X-ray crystallography and molecular dynamics studies. Comparison of conformations observed in single crystals with several reported co-crystals of protein–drug complexes suggests existence of two conserved conformations of Imatinib, extended and compact (or folded), corresponding to two binding modes of interaction with the receptor. Furthermore, these conformations are conserved throughout a dynamics simulation. The present study attempts to draw a parallel on conformations and binding patterns of interactions, obtained from small-molecule single-crystal and macromolecule co-crystal studies, and provides structural insights for understanding the high selectivity of this drug molecule.

► Structure and dynamics of Leukemia drug, Imatinib (Gleevec) were examined. ► Imatinib conformations in various crystals and simulation were compared. ► Imatinib possesses conserved conformations in different environment. ► Study provides structural insight to understand high selectivity of drugs.