Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydrogen bonds, which are critical for the forming of the diacylglycerols/phorbol esters binding site, and indicates the important role of Gln27 for the geometry of this site. According to the model, PMA interacts with the C1B domain by hydrophobic interactions with Pro11 and Tyr22 and by three persistent hydrogen bonds between the C3 carbonyl group of PMA and Gly23 and between the C20 hydroxyl group of PMA and the Leu21 and Thr12 residues of the C1B domain. The C9 hydroxyl group of PMA does not interact with the C1B domain, but it is involved in the interaction with the DPPC bilayer. Two preferential orientations of the C1B-PMA complex toward the DPPC bilayer resulted from our molecular modeling study.