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Sensitivity of the folding/unfolding transition state ensemble of chymotrypsin inhibitor 2 to changes in temperature and solvent
Author(s) -
Day Ryan,
Daggett Valerie
Publication year - 2005
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.041226005
Subject(s) - chemistry , molecular dynamics , folding (dsp implementation) , protein folding , sensitivity (control systems) , thermodynamics , denaturation (fissile materials) , chemical physics , transition temperature , native state , transition state , crystallography , computational chemistry , physics , organic chemistry , condensed matter physics , catalysis , biochemistry , superconductivity , electronic engineering , electrical engineering , nuclear chemistry , engineering
To better characterize the transition state for folding/unfolding and its sensitivity to environmental changes, we have run multiple molecular dynamics simulations of chymotrypsin inhibitor 2 (CI2) under varying solvent conditions and temperature. The transition state structures agree well with experiment, and are similar under all of the conditions investigated here. Increasing the temperature leads to some movement in the position of the transition state along several reaction coordinates, as measured by changes in properties of the transition state structures. These structural changes are in the direction of a more native‐like transition state as denaturation conditions become more severe, as expected for a Hammond effect. These structural changes are not, however, reflected in the global structure as measured by the total number of contacts or the average S‐values. These results suggest that the small changes in average Φ‐values with temperature seen by experiment may be due to an increase in the sensitivity of the transition state to mutation rather than a change in the average structure of the transition state. A simple analysis of the rates of unfolding indicates that the free energy barrier to unfolding decreases with increasing temperature, but even in our very high temperature simulations there is a small free energy barrier.