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The conformational change of α-chymotrypsin from an inactive, chymotrypsinogen like structure at high pH to an active conformation around pH 8.5 is used here as a model system to generate possible pathways for the transition by use of two different theoretical methods. One method, the 'targeted molecular dynamics' algorithm (TMD) adds a constraint in the direction of the target to a molecular dynamics force field and gives two different paths, one for every direction of the reaction (Schlitter,J., Engles,M., Kruger,P.J., MOl. Graphics (1994) 12, 84-89). The second method, the 'self penalty walk' algorithm (SPW), refines an initially guessed path by minimizing the sum of the energies of its structures (Elber,R. and Karplus,M., Chem. Phys. Lett. (1987) 139, 375-380). Thus, starting for a linear path as a first approximation, it produces a reaction coordinate of the transition. The structures of the TMD and SPW paths are similar only in the beginning while the middle part of the SPW path links the two TMD branches. The activation of α-chymotrypsin in the TMD path starts with a movement of loop VII (residues 215-225), pulling on loop VI (residues 186-194). Then the side chain of Met192 turns to the surface and Ile16 approaches Asp194 to form a salt bridge. In the TMD deactivation path, loop VII also moves and pushes loop VI to the protein core. The Met192 side chain adopts three intermediate conformations, till the salt bridge Ile16-Asp194 is broken and loop VI rearranges to its final conformation. In the SPW pathway both the formation of the salt bridge and the movement of Met192 happen simultaneously between two consecutive steps.Key words: conformational change/protein/pathway calculation/GROMOS/CHARMM