Ras farnesyltransferase catalyzes the carboxyl-terminal farnesylation of Ras as well as other proteins involved in signal transduction processes. Previous studies demonstrated that its inhibition suppresses the activity of Ras transformed phenotypes in cultured cells, causing tumor regression in animal models. This observation led to the consideration of farnesyltransferase as a target for cancer therapy. In the present work we report the results of a computational study aimed at assessing the bioactive conformation of the peptide Cys-Val-Phe-Met, known to be the minimum peptide sequence that inhibits farnesyltransferase. For this purpose the conformational preferences of four analogs of the peptide were assessed by means of thorough searches of their respective conformational spaces, using a simulated annealing protocol as sampling technique. Specifically, two active analogs: Cys-Val-Tic-Met and Cys-Val-psi(CH2NH)Tic-Met and two inactive analogs: Cys-Val-Tic-psi(CH2NH)Met and Cys-Val-Aic-Met were selected for the present study. Low energy conformations of the four analogs were classified according to their structural motifs. The putative bioactive conformation of the minimum farnesyltransferase recognition motif was assessed by cross-comparison of the different classes of conformations obtained for the two active and the two inactive analogs. The putative bioactive conformation is characterized by two structural motifs: i) a C14 pseudo-ring stabilized by a hydrogen bond between the amino group of Cys1 and the carboxylate group of Met4 and a C11 pseudo-ring involving the residues Cys1 and Tic3. In addition, the thiol group of Cys1 side chain of the bioactive conformation points to the carboxylate moiety of Met4.