Free-energy landscape of a chameleon sequence in explicit water and its inherent alpha/beta bifacial property.
A sequence in yeast MATalpha2/MCM1/DNA complex that folds into alpha-helix or beta-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 alpha or beta structure: The conformational distribution in the landscape consisted of two alpha-helical clusters with different packing patterns of hydrophobic residues, and four beta-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 alpha-beta transitions. Additional unfolding simulations done with replacing amino acids showed that the chameleon sequence has an advantage to form an alpha-helix. Current study may be useful to understand the mechanism of diseases resulting from abnormal chain folding, such as amyloid disease.
Ikeda
Kazuyoshi
K
Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo 135-0064, Japan.
Higo
Junichi
J
D000595:Amino Acid Sequence; D004271:DNA, Fungal / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry*; D018398:Homeodomain Proteins / Q000737:chemistry; D007700:Kinetics; D026341:Minichromosome Maintenance 1 Protein / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry; D015003:Yeasts / Q000235:genetics
D004271:DNA, Fungal; D005656:Fungal Proteins; D018398:Homeodomain Proteins; D026341:Minichromosome Maintenance 1 Protein; D010446:Peptide Fragments; D012097:Repressor Proteins; D014867:Water