期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：20
页码：7606-7611
DOI：10.1073/pnas.0308497101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Site-specific information about structural heterogeneities of the protein-folding transition-state ensemble is commonly derived from the scatter of the Bronsted plot through the individual values of {phi}={Delta}logkf/{Delta}logKD-N. Here, we provide a second level of site-specific detail in the transition-state analysis by demonstrating that the scatter of the Hammond plot is related to heterogeneities in the {phi}-value growth. That is, the extent of transition-state movement ({Delta}{beta}{ddagger}) is proportional to the free-energy gradient of the mutational perturbation across the top of the activation barrier, {phi}'({beta}{ddagger}) {propto} {Delta}logKD-N. The analysis is applied to the two-state protein L23 where the site-specific free-energy gradients are used to identify the interactions that show the highest degree of consolidation after crossing the barrier top. These interactions are distributed as a shell around the high-{phi} initiation point and denote the side-chain contacts that add criticality to the folding nucleus.
关键词：transition state ; protein engineering ; φ-value analysis ; Brønsted plot ; Hammond behavior
