Free-energy landscape of a chameleon sequence in explicit water and its inherent α/β bifacial property

摘要

A sequence in yeast MATα2/MCM1/DNA complex that folds into α-helix or β-hairpin depending on the surroundings has been known as "chameleon" sequence. We obtained the free-energy landscape of this sequence by using a generalized-ensemble method, multicanonical molecular dynamics simulation, to sample the conformational space. The system was expressed with an all-atom model in explicit water, and the initial conformation for the simulation was a random one. The free-energy landscape demonstrated that this sequence inherently has an ability to form either α or β structure: The conformational distribution in the landscape consisted of two α-helical clusters with different packing patterns of hydrophobic residues, and four β-hairpin clusters with different strand–strand interaction patterns. Narrow pathways connecting the clusters were found, and analysis on the pathways showed that a compact structure formed at the N-terminal root of the chameleon sequence controls the cluster-cluster transitions. The free-energy landscape indicates that a small conditional change induces α-β transitions. Additional unfolding simulations done with replacing amino acids showed that the chameleon sequence has an advantage to form an α-helix. Current study may be useful to understand the mechanism of diseases resulting from abnormal chain folding, such as amyloid disease.