Why are proteins marginally stable?

By D. Taverna, Richard A. Goldstein. 2002

345 citations recorded by the source corpus.

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Citations in the corpus

Exploring protein fitness landscapes by directed evolution (2009, neutral): “The first is the low overall density of functional sequences: the vast majority do not code for any functional protein, much less the desired protei”
A biophysical protein folding model accounts for most mutational fitness effects in viruses (2011, positive): “N and m. Each instance of p(G) vanishes at G=0, peaks when -G equals a few kcal/mole, and decays for more negative G. These qualitative features agree with previous work (analytic and simulation) (19, 28, 29) as well as the empirical distribution sampled from different genes and organisms in all kin”
Protein stability imposes limits on organism complexity and speed of molecular evolution (2007, background): “ly when λ≥0 which imposes an upper bound Γ* on the number of genes of an organism at a given mutational load: () () * 2 22 2 2 max min 2 1 mm d bb bh hD hDEE π ΓΓ <=− + + + − (8) Note that m b Γ is simply the number of mutations per portion of the genome encoding essential genes per replica”
Optimizing protein stability in vivo. (2009, background): “…by the destabilizing effects of random mutation, which may act to decrease a protein’s stability until it reaches a 868 Molecular Cell 36, 861–871, December 11, 2009 ª2009 Elsevier threshold value below which function begins to be affected (Bloom et al., 2006, 2007; Taverna and Goldstein, 2002).”
Merging molecular mechanism and evolution: theory and computation at the interface of biophysics and evolutionary population genetics (2014, background): “As discussed here and in [9,11,19,20,24,25 (cid:2) ,26 (cid:2) ,85 (cid:2)(cid:2) ], selection for folding stability should not lead to most stable proteins.”
Inferring Stabilizing Mutations from Protein Phylogenies: Application to Influenza Hemagglutinin (2009, neutral): “We begin by introducing a conceptual framework that relates the probability that a specific amino acid mutation will be selectively neutral (and so have an opportunity to spread by genetic drift) to its effect on protein stability. Because ”
Stability-mediated epistasis constrains the evolution of an influenza protein (2013, background): “…that evolution only selects against insufficient stability, but that proteins typically are marginally stable because most mutations are destabilizing and so extra stability is rapidly eroded by functionally neutral but destabilizing mutations (Taverna and Goldstein, 2002; Bloom et al., 2007).”
Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites (2014, background): “…level (Drummond & Wilke 2008, Serohijos et al. 2012), the evolution of novel function (Bloom et al. 2006, Tokuriki et al. 2008), and the expected equilibrium distributions of stability and the explanation of marginal stability (Taverna & Goldstein 2002, Goldstein 2011, Wylie & Shakhnovich 2011).”