Experimental evidence indicates that proteins are marginally stable. Unlike all previous proposals here we suggest, on a statistical thermodynamics basis, that the upper bound of the marginal stability of proteins also belongs to biomacromolecular complexes and its origin should be sought on fluctuations of the pairwise and many-body interactions on both the macro-molecules and the solvent. In other words, at the global minimum of the free energy all folding dominant forces are almost compensated in a state of quasi-equilibrium where the structures preserve their biological activity. Thus, mutations disrupting this equilibrium beyond the protein marginal stability upper bound ( 7.4 kcal/ mol) will be subject to negative selection and mutations that preserve it will be neutral or nearly neutral , with respect to the marginal stability. Although, proteins can still evolve under the influence of natural selection .
Here we propose that the upper bound marginal stability of proteins ( 7.4 kcal/ mol) is a universal property that includes macro-molecular complexes and is not affected by molecular changes such as mutations and Post-Translational Modifications. Its existence is, essentially, a consequence of the Anfinsen thermodynamic hypothesis rather than a result of an evolutive process. This result enables us to conjecture that neutral evolution should also be , with respect to protein stability, a universal phenomenon .
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Experimental evidence indicates that proteins are marginally stable. Unlike all previous proposals here we suggest, on a statistical thermodynamics basis,
Here we propose
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of the
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also belongs to biomacromolecular complexes and its origin should be sought on fluctuations of the pairwise and many-body interactions on both the macro-molecules and the solvent. In other words, at the global minimum of the free energy all folding dominant forces are almost compensated in a state of quasi-equilibrium where the structures preserve their biological activity. Thus, mutations disrupting this equilibrium beyond the protein marginal stability upper bound (
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mol) will be subject to negative selection and mutations that preserve it will be neutral or nearly neutral
mol) is a universal property that includes macro-molecular complexes and is not affected by molecular changes such as mutations and Post-Translational Modifications. Its existence is, essentially, a consequence of the Anfinsen thermodynamic hypothesis rather than a result of an evolutive process. This result enables us to conjecture that neutral evolution should also be
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the marginal stability. Although, proteins can still evolve under the influence of natural selection
protein stability, a universal phenomenon