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：2002
卷号：99
期号：3
页码：1309-1313
DOI：10.1073/pnas.032665499
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：There is a paradox concerning the {beta} propensities of the amino acids: the amino acids with the highest {beta} propensities such as valine and isoleucine have the highest tendency to desolvate the peptide backbone, which should result in a loss of stability. Nevertheless, backbone solvation, calculated as electrostatic solvation free energy (ESF), is highly correlated with mutant stability in the zinc-finger system studied by Kim and Berg [Kim, C. A. & Berg, J. M. (1993) Nature (London) 362, 267-270], and valine and isoleucine are among the most stabilizing amino acids. This inverse correlation between stability and ESF can be explained, because the mutant ESF differences in the unfolded protein are larger than in the native protein. Consequently, mutations such as Ala to Val destabilize the unfolded form more than the native protein. By comparing mutant {Delta}ESF values in isolated {beta}-strands versus {beta}-sheets, we conclude that amino acids with high {beta} propensities should exert their stabilizing effects at early stages in folding. This deduction agrees with the studies by Clarke and coworkers [Lorch, M., Mason, J. M., Clarke, A. R. & Parker, M. J. (1999) Biochemistry 38, 1377-1385, and Lorch, M., Mason, J. M., Sessions, R. B. & Clarke, A. R. (2000) Biochemistry 39, 3480-3485] of the thermodynamics of folding of the {beta}-sheet protein CD2.d1.
