Molecular models of phytochrome were generated to gain insight into structure-function relationships of this important, tetrapyrrole-containing plant protein. Molecular dynamics simulation of a 51-amino acid segment surrounding the chromophore attachment site in oat phytochrome (Cys-321) generated a folded structure. Cys-321 was located within this structure in a beta-turn at the entrance of a distinct pocket. When attached to this amino acid, a semicircular conformation of the Pr chromophore easily fit within the pocket, with the sidechain carboxyl groups in association with Arg and Lys residues in the peptide backbone. Models of Z and E isomers at the C-4 or C-15 double bonds were generated to produce potential conformations of the Pfr chromophore. Comparison of predicted reactivity of the tetrapyrrole, deduced from the models, with that described in the extensive literature on phytochrome clearly indicated that isomerization at C-4 is consistent with experimental data. Isomerization at C-4 caused the chromphore to move partially out of the pocket and brought the sidechain carboxyl groups and ring D to the surface of the polypeptide. This change in orientation is compatible with the observed interaction of Pfr with metal ions, which possibly is a component in the physiological activity of this protein.