Premium
The effect of amino acid substitution on protein‐folding and ‐unfolding transition studied by computer simulation
Author(s) -
Taketomi Hiroshi,
Kanô Fumiaki,
Gō Nobuhiro
Publication year - 1988
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360270402
Subject(s) - chemistry , arrhenius plot , thermodynamics , intramolecular force , kinetic energy , protein folding , contact order , conformational entropy , entropy (arrow of time) , folding (dsp implementation) , relaxation (psychology) , logarithm , transition temperature , arrhenius equation , crystallography , activation energy , native state , stereochemistry , molecule , organic chemistry , physics , mathematics , mathematical analysis , engineering , psychology , social psychology , biochemistry , quantum mechanics , superconductivity , electrical engineering
Protein‐folding and ‐unfolding transitions were studied by the method of computer simulation. The protein was modeled as a two‐dimensional lattice polymer. Various energy terms were assumed to be operative between units composing the polymer. But hydrophobic interactions were neglected explicitly. Both thermodynamic and kinetic quantities were obtained from the simulation, and from their temperature dependence in the transition zone characteristics of the conformational transition of proteins were discussed. Two amino acid substituted models, differing in the location of substitution, were studied and compared with the original in order to clarify the effect of substitution on conformational transition of proteins. The following conclusions were reached in this study: (1) The relaxation time of the slow mode, which reflects the overall folding and unfolding processes, shows a peak near the transition temperature, while that of the fast mode is almost independent of temperature. The peak of the slow mode occurs at a slightly lower temperature than the transition temperature. (2) The dependence of the logarithm of the rate constants on the inverse of temperature (Arrhenius plot) is linear. Therefore, the plot of the free energy of activation vs temperature is linear. (3) The values of kinetic parameters obtained suggest that in the activated state the intramolecular interactions are half broken, while the state is close to the native state on the entropy axis. (4) The amino acid substitution, which is modeled as having slightly unfavorable short‐range interactions, causes the substituted ones to be slightly unstable. Moreover, it causes the folding transition to slow. From the analysis of the way slowing down is observed in the two substituted models, we conclude that a structure, designed to model a β‐sheet, is formed before it gets assembled with other structures, which are designed to model α‐helices. The process of assembly occurs nearly at the activated state of the folding and unfolding transition. (5) It is suggested from this study that the maximum of folding rate constant in the Arrhenius plot that has been observed experimentally in real proteins is likely due to hydrophobic interactions.