Protein kinase A (PKA) and protein kinase C (PKC) are potential targets in treating tumour and their over expression leads to cellular proliferation and differentiation abnormally. BD2 is a high selective inhibitor for PKA over PKC. In order to elucidate the mechanism of the high selectivity of BD2, in this paper, using the crystal structure of PKA complexed with BD2 as the template, model of PKC βII was built by homology modeling and its complex with BD2 was constructed by molecular docking. 2.5 ns molecular dynamics simulations were carried out on PKA-BD2 complex and PKC-BD2 complex. The binding energy of BD2 with PKA and PKC was calculated by MM-GBSA method, and the interaction between BD2 with the key residues of the two protein kinases was evaluated by energy decomposition analysis. The result of binding energy can described the experimental phenomenon that BD2 is high selective inhibitor for PKA over PKC. The difference of the interaction of B ring and acidamide of BD2 with PKA and PKC was evaluated by hydrogen bond analysis and energy decomposition analysis, which is intrinsic factor for selectivity of BD2. The mechanism of the high selectivity of BD2 was elucidated, which provides the basis for designing and optimizing balanol analogue inhibitor.

Key words: protein kinase A (PKA), protein kinase C (PKC), homology modeling, molecular docking, molecular dynamics simulation, inhibition selectivity