Protein Structure Prediction: Assembly of Secondary Structure Elements by Basin‐Hopping

The 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.