AbstractThe prediction of protein tertiary structure from primary structure remains a challenging task. One possible approach to this problem is the application of basin‐hopping global optimization combined with an all‐atom force field. In this work, the efficiency of basin‐hopping is improved by introducing an approach that derives tertiary structures from the secondary structure assignments of individual residues. This approach is termed secondary‐to‐tertiary basin‐hopping and benchmarked for three miniproteins: trpzip, trp‐cage and ER‐10. For each of the three miniproteins, the secondary‐to‐tertiary basin‐hopping approach successfully and reliably predicts their three‐dimensional structure. When it is applied to larger proteins, correctly folded structures are obtained. It can be concluded that the assembly of secondary structure elements using basin‐hopping is a promising tool for de novo protein structure prediction.