期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 97, 期 2, 页码 634-639出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.97.2.634
关键词
protein folding; Phi values; folding funnels; folding landscapes
资金
- NIGMS NIH HHS [T32 GM008326] Funding Source: Medline
- PHS HHS [T32 GN08326] Funding Source: Medline
We present a method for determining structural properties of the ensemble of folding transition states from protein simulations. Th is method relies on thermodynamic quantities (free energies as a function of global reaction coordinates, such as the percentage of native contacts) and not on kinetic measurements (rates, transmission coefficients, complete trajectories); consequently, it requires fewer computational resources compared with other approaches, making it more suited to large and complex models, We explain the theoretical framework that underlies this method and use it to clarify the connection between the experimentally determined Phi value, a quantity determined by the ratio of rate and stability changes due to point mutations, and the average structure of the transition state ensemble. To determine the accuracy of this thermodynamic approach, we apply it to minimalist protein models and compare these results with the ones obtained by using the standard experimental procedure for determining Phi values. We show that the accuracy of both methods depends sensitively on the amount of frustration. In particular, the results are similar when applied to models with minimal amounts of frustration, characteristic of rapid-folding, single-domain globular proteins.
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