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.
Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo 135-0064, Japan.
Kazuyoshi
K
Ikeda
Junichi
J
Higo
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