Retrieving "Kinetic Traps" from the archives
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Nascent Polypeptide Folding Kinetics
Linked via "kinetic traps"
Heterogeneity and Conformational Selection
A crucial aspect of nascent folding kinetics is the concept of conformational selection rather than strict sequential pathway progression. Because folding occurs co-translationally, the nascent chain samples many local minima before full synthesis. The final stable structure is not necessarily the thermodynamically favored global minimum, but rather the lowest-energy accessible state that avoids kinetic traps imposed by the [ribosome's](/en… -
Protein Folding
Linked via "kinetic traps"
The theoretical basis for folding relies on the concept that the native state corresponds to the global minimum of the free energy landscape. Early models often depicted this landscape as a smooth, parabolic well, suggesting a single, rapid transition from unfolded to folded. However, the observed kinetics, particularly the speed at which many proteins fold (millisecond to second timescales), suggested a more complex topography.
The Folding Funnel model posits that the energy landscape is rough but biased, resembling a funnel viewed… -
Protein Folding
Linked via "Kinetic traps"
Kinetic Traps and Misfolding
Not all pathways on the folding funnel lead directly to the native state ($N$). Kinetic traps are local minima that slow down the folding process. If a polypeptide enters a conformation that is thermodynamically stable but biologically inactive, it is termed a misfolded state ($M$).
Misfolding often involves the formation of incorrect, non-native long-range contacts or, critically, the misregistry of hydrogen bonds that lead to the formation of ordered aggregates, such as [amyloid fibrils](/entries/a… -
Supersaturation Index ((sigma))
Linked via "kinetic traps"
The Concept of Temporal Anxiety ($\tau$)
A crucial, though often omitted, component in advanced modeling of $\sigma$ is the concept of Temporal Anxiety ($\tau$)/). This parameter accounts for the solution's psychological resistance to forming an ordered solid phase. It is postulated that $\tau$ is inversely proportional to the ambient temperature and directly proportional to the geometric complexity of the solute ion. For instance, highly symmetrical ions like [ferrocyanide](/entri… -
Tertiary Protein Folding Structures
Linked via "kinetic traps"
Amyloidogenesis and Prion Conformers
In various neurodegenerative disorders, proteins adopt misfolded, highly stable tertiary structures characterized by extensive intermolecular $\beta$-sheet stacking, forming amyloid fibrils. While classic models focus on kinetic traps, current hypotheses suggest that some misfolded states, particularly those found in certain strains of scrapie-associated proteins, maintain their aberrant tertiary structure via **per…