Palbociclib (PD 0332991) Interaction with Kinases. Theoretical and Comparative Molecular Docking Study

The optimized geometry of palbociclib, (PD 0332991) (8-cyclopentyl-6-ethanoyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one), electrostatic potential map, molecular orbitals were calculated using the density functional theory. The geometry was used in a molecular docking study of palbociclib-kinase complexes, results could be explained by the charge of the nitrogen and oxygen atoms within the palbociclib. Energy gap of HOMO-LUMO surfaces, could help to explain the reactivity of the ligand and the hydrogen bonding with three different kinases, two of CDK6 and one of CDK4 type. Docking results are similar and complementary with literature reports using molecular dynamics, were hydrogen bonding was obtained and analyzed. The promiscuity of three kinases with palbociclib was detected by the docking results, thus, palbociclib could be used in other types of cancer besides myeloid leukemia. Some similarities are found with CDK4/CDK6 kinases which allow us to determine that palbociclib could be used to control other resistant inhibitor types of cancer.

Automated summary

The optimized geometry, electrostatic potential map, and molecular orbitals of palbociclib were calculated using density functional theory. Molecular docking of palbociclib-kinase complexes using the calculated geometry revealed the importance of nitrogen and oxygen atom charges in the binding. The docking results, similar to literature reports using molecular dynamics, showed the promiscuity of palbociclib with three different kinases and its potential use in other types of cancer.