Protein farnesyltransferase (FTase) is a particularly interesting zinc enzyme that promotes the transfer of a 15-carbons isoprenoid farnesyl group from farnesyl diphosphate (FPP) to a number of peptide substrates with a typical-CAAX motif at the carboxyl-terminus, where C represents the cysteine residue that is farnesylated. This enzyme has been the subject of great attention in anticancer research, as several proteins known to be involved in human cancer development are thought to serve as substrates for FTase and to require farnesylation for proper biological activity. Several FTase inhibitors have advanced into clinical testing. However, despite the progress in the field several functional and mechanistic doubts on the FTase catalytic activity have persisted. This work describes the application of molecular dynamics simulations using specifically designed molecular mechanical parameters to the four key-intermediate states formed during the FTase catalytic mechanism-FTase resting state, binary complex (FTase-FPP), ternary complex (FTase-FPP-Peptide), and product complex (FTase-Product). The study involves a comparative analysis of several important molecular aspects for which are vital not only motion but also the conformational sampling of both enzyme and substrate as well as their interaction, and especially the effect of the solvent. These include the radial distribution function of the water molecules around the catalytically important zinc metal atom, the conformations of the substrate and product molecules and the corresponding RMSF values, critical hydrogen bonds and several catalytically relevant distances. These results are discussed in light of recent experimental and computational evidence, yielding new insights into the elusive catalytic mechanism of this enzyme.