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

Publisher Website
Google Scholar
Abstract
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.