The diagram sketches how proteins fold into their native structures by minimizing their free energy.
The folding funnel hypothesis is a specific version of the energy landscape theory of protein folding, which assumes that a protein's native state corresponds to its free energy minimum under the solution conditions usually encountered in cells. Although energy landscapes may be "rough", with many non-native local minima in which partially folded proteins can become trapped, the folding funnel hypothesis assumes that the native state is a deep free energy minimum with steep walls, corresponding to a single well-defined tertiary structure. The term was introduced by Ken A. Dill in a 1987 article discussing the stabilities of globular proteins.[1]
The folding funnel hypothesis is closely related to the hydrophobic collapse hypothesis, under which the driving force for protein folding is the stabilization associated with the sequestration of hydrophobic amino acid side chains in the interior of the folded protein. This allows the water solvent to maximize its entropy, lowering the total free energy. On the side of the protein, free energy is further lowered by favorable energetic contacts: isolation of electrostatically charged side chains on the solvent-accessible protein surface and neutralization of salt bridges within the protein's core. The molten globule state predicted by the folding funnel theory as an ensemble of folding intermediates thus corresponds to a protein in which hydrophobic collapse has occurred but many native contacts, or close residue-residue interactions represented in the native state, have yet to form.[citation needed]
In the canonical depiction of the folding funnel, the depth of the well represents the energetic stabilization of the native state versus the denatured state, and the width of the well represents the conformational entropy of the system. The surface outside the well is shown as relatively flat to represent the heterogeneity of the random coil state. The theory's name derives from an analogy between the shape of the well and a physical funnel, in which dispersed liquid is concentrated into a single narrow area.
^Dill, Ken A. (1987). Oxender, DL; Fox, CF (eds.). "The stabilities of globular proteins". Protein Engineering. New York: Alan R. Liss, Inc.: 187–192.
The foldingfunnel hypothesis is a specific version of the energy landscape theory of protein folding, which assumes that a protein's native state corresponds...
unfolded state may form a folding initiation site and guide the subsequent folding reactions. The duration of the folding process varies dramatically...
fold flat. The term "funnel" may refer to the chimney or smokestack on a steam locomotive and commonly refers to the same on a ship. The term funnel is...
contributing to the thermodynamic favourability of a folded polypeptide. As can be seen in the foldingfunnel diagram, the polypeptide is at its highest energy...
partially folded structures through which a protein passes on its way to the folded structure. This has been described in terms of a foldingfunnel, in which...
folded proteins (hence the "molten"). Protein folding is navigated by a dynamic interplay of secondary and tertiary interactions. Two extreme folding...
Look up filter funnel in Wiktionary, the free dictionary. A filter funnel is a laboratory funnel used for separating solids from liquids via the laboratory...
It is a key prediction of the foldingfunnel hypothesis of the energy landscape theory of proteins. Downhill folding is predicted to occur under conditions...
The key concept in the energy landscape approach to protein folding is the foldingfunnel hypothesis. In catalysis, when designing new catalysts or refining...
debate. The most widely accepted common name for members of the family is funnel weaver. The body length of the smallest Agelenidae spiders are about 4 mm...
one of a number of families and genera of spiders known as tunnelweb or funnel-web spiders. In 2018, the family was substantially reduced in size by genera...
Tamura, Atsuo & Takada, Shoji (2003). "De Novo Design of Foldable Proteins with Smooth FoldingFunnel: Automated Negative Design and Experimental Verification"...
trapdoors over their burrows. Other prominent groups include Australian funnel web spiders and tarantulas, with the latter accounting for around one third...
kinetics of folding can be explored, and this may provide insights into the folding of real proteins. Some of the examples include study of folding processes...
thought to fold faster and some may be candidates for downhill folding. Taketomi, H.; Ueda, Y.; Gō, N. (1975). "Studies on protein folding, unfolding...
In mass spectrometry, an ion funnel is a device used to focus a beam of ions using a series of stacked ring electrodes with decreasing inner diameter....
Dwarf tarantulas, also known as sheet funnel-web spiders are a type of spider from the family Mecicobothriidae. Dwarf tarantulas are one of several families...
are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded. Though the binding...
struggle of trapped prey to lure the host closer. Pholcids prey on Tegenaria funnel weaver spiders, and are known to attack and eat redback spiders, huntsman...
members include the notorious Sydney funnel-web spider, and their spinnerets appear adapted for building funnel-shaped webs to catch jumping insects....
with other members of the order Mygalomorphae, such as trapdoor spiders, funnel-web spiders and purseweb spiders. They can also be confused with some members...
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