AbstractAn extended simulated annealing process (ESAP) has been developed in order to obtain an ensemble of conformations of a peptide segment from a protein fluctuating at a given temperature. The annealing process was performed with a fast Monte Carlo method using the scaled collective variables developed by Noguti and Gō. The system was divided into two parts: one consists of one or more peptide segments and is flexible around the main‐chain and side‐chain torsional angles; the other represents the rest of the molecule and was maintained fixed at the atomic positions determined by x‐ray experiments. The target function included the nonbonding atomic interactions and a distance function to anchor the N and C terminal ends of each segment to the fixed part. Three systems of complementary determining regions (CDR) of antibodies were tested and compared to x‐ray data: L2 loop (7 residues) of the light chain of α‐type Bence‐Jones protein, H1 and the H2 loops (14 residues) of McPC603, and H1 and H2 loops (12 residues) of HyHEL‐5. Each state of CDR conformations was characterized at room temperature by the average of their coordinates (average conformation) and the internal energy. With a limited number of annealing processes (10), starting from the extended conformation, we have obtained states with conformations close to the observed x‐ray structures, from 1.1 to 1.7 Å root mean square deviation (rmsd) of main‐chain atoms depending on the system. These states were identical or within 0.25 Å rmsd of those of lowest internal energy. For unknown CDR structures the criteria of lowest internal energies from ESAP can be used to predict hypervariable loop structures in antibodies with an accuracy compar