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Forces stabilizing proteins
Journal article   Open access   Peer reviewed

Forces stabilizing proteins

C. Nick Pace, J. Martin Scholtz and Gerald R. Grimsley
FEBS letters, Vol.588(14), pp.2177-2184
06/27/2014
DOI: 10.1016/j.febslet.2014.05.006
PMCID: PMC4116631
PMID: 24846139
url
https://doi.org/10.1016/j.febslet.2014.05.006View
Published (Version of record) Open Access

Abstract

The goal of this article is to summarize what has been learned about the major forces stabilizing proteins since the late 1980s when site‐directed mutagenesis became possible. The following conclusions are derived from experimental studies of hydrophobic and hydrogen bonding variants. (1) Based on studies of 138 hydrophobic interaction variants in 11 proteins, burying a –CH2− group on folding contributes 1.1 ± 0.5 kcal/mol to protein stability. (2) The burial of non‐polar side chains contributes to protein stability in two ways: first, a term that depends on the removal of the side chains from water and, more importantly, the enhanced London dispersion forces that result from the tight packing in the protein interior. (3) Based on studies of 151 hydrogen bonding variants in 15 proteins, forming a hydrogen bond on folding contributes 1.1 ± 0.8 kcal/mol to protein stability. (4) The contribution of hydrogen bonds to protein stability is strongly context dependent. (5) Hydrogen bonds by side chains and peptide groups make similar contributions to protein stability. (6) Polar group burial can make a favorable contribution to protein stability even if the polar group is not hydrogen bonded. (7) Hydrophobic interactions and hydrogen bonds both make large contributions to protein stability.
Conformational entropy Hydrogen bonds Hydrophobic interactions Protein stability

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