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Is there a unique melting temperature for two‐state proteins?
Author(s) -
Klimov D. K.,
Thirumalai D.
Publication year - 2001
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.10005
Subject(s) - cooperativity , scaling , chemistry , melting temperature , protein folding , thermodynamics , chemical physics , crystallography , folding (dsp implementation) , thermal , physics , materials science , mathematics , biochemistry , geometry , electrical engineering , composite material , engineering
Thermal unfolding (or folding) in many proteins occurs in an apparent two‐state manner, suggesting that only two states, unfolded and folded, are populated. At the melting temperature, T m , the two states coexist. Using lattice models with side chains we show that individual residues become structured at temperatures that deviate from T m , which implies that partially folded conformations make substantial contribution to thermodynamic properties of two‐state proteins. We also find that the folding cooperativity for a given residue is linked to its accessible surface area. These results are consistent with the experiments on GCN4‐like zipper peptide, which showed that local melting temperatures differ from T m . Analysis of thermal unfolding of six proteins shows that Δ T / T m ∼ N −1 , where Δ T is the transition width and N is the number of residues. This scaling allows us to conclude that, when corrected for finite size effects, folding cooperativity can be captured using coarse grained models. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 161–165, 2002