Diffusion–collision model for protein folding

Karplus, Martin; Weaver, D. L.

doi:10.1002/bip.1979.360180608

Cited by 188 publications

(123 citation statements)

References 24 publications

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“…This is very close to the framework model [76] or diffusion collision-picture [78][79][80][81][82] that was so often thought to describe protein folding. In the original versions of such models, only correct structures are formed initially and these can dock to form completed structures.…”

Section: The Phase Diagram and Protein Folding Scenariossupporting

confidence: 72%

Funnels, pathways, and the energy landscape of protein folding: A synthesis

et al. 1995

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The understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation, that is, to the energy landscape. The statistical energy landscape approach explains when and why unique behaviors, such as specific folding pathways, occur in some proteins and more generally explains the distinction between folding processes common to all sequences and those peculiar to individual sequences. This approach also gives new, quantitative insights into the interpretation of experiments and simulations of protein folding thermodynamics and kinetics. Specifically, the picture provides simple explanations for folding as a two‐state first‐order phase transition, for the origin of metastable collapsed unfolded states and for the curved Arrhenius plots observed in both laboratory experiments and discrete lattice simulations. The relation of these quantitative ideas to folding pathways, to uniexponential vs. multiexponential behavior in protein folding experiments and to the effect of mutations on folding is also discussed. The success of energy landscape ideas in protein structure prediction is also described. The use of the energy landscape approach for analyzing data is illustrated with a quantitative analysis of some recent simulations, and a qualitative analysis of experiments on the folding of three proteins. The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions. © 1995 Wiley‐Liss, Inc.

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Section: The Phase Diagram and Protein Folding Scenariossupporting

confidence: 72%

Funnels, pathways, and the energy landscape of protein folding: A synthesis

et al. 1995

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“…In the diffusion-collision model, microdomain structures form first and then diffuse and collide to form larger structures (115,116). The nucleationcondensation mechanism (70) proposes that a diffuse transition state ensemble (TSE) with some secondary structure nucleates tertiary contacts.…”

Section: Are There Mechanisms Of Protein Folding?mentioning

confidence: 99%

Protein Folding Problem

2008

Encyclopedia of Public Health

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The "protein folding problem" consists of three closely related puzzles: (a) What is the folding code? (b) What is the folding mechanism? (c) Can we predict the native structure of a protein from its amino acid sequence? Once regarded as a grand challenge, protein folding has seen great progress in recent years. Now, foldable proteins and nonbiological polymers are being designed routinely and moving toward successful applications. The structures of small proteins are now often well predicted by computer methods. And, there is now a testable explanation for how a protein can fold so quickly: A protein solves its large global optimization problem as a series of smaller local optimization problems, growing and assembling the native structure from peptide fragments, local structures first.

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“…One view is that local context dominates and folding proceeds by the assembly of preformed hydrogen-bonded elements (6). At the other extreme is a hydrophobic collapse with minimal 2°structure.…”

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confidence: 99%

Revealing what gets buried first in protein folding

Sosnick

Baxa

2013

Proc. Natl. Acad. Sci. U.S.A.

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After decades of research, the nature of the rate-limiting step in the folding of globular proteins still elicits a range of opinions (1). The properties of the associated transition state (TS) provide critical insights into possible folding mechanisms. However, the characterization of the TS is challenging because atomic level methods cannot be applied to this minimally populated state, and lower resolution methods have produced divergent views. Even the existence of a generalized TS remains actively debated. In PNAS, Guinn et al. (2) dissect the burial properties of the TS for 13 proteins by analyzing the denaturant and temperature dependence of folding rates to distinguish the burial of hydrophobic surface from that of amide groups. With this capability, they propose that the TSs generally are very advanced and often contain the native 2°s tructure, a level higher than most prior methods have indicated.The analysis by Guinn et al. (2) indicates that amide surface is preferentially buried in the TS. On average, 77% of the total amide surface is buried in the TS, whereas a smaller fraction, 60%, of the total hydrophobic surface is buried at this point in the reaction (although ∼twofold more hydrophobic surface is buried in the TS in absolute terms). Notably, the amount of amide burial often can be accounted for through the formation of the entire native 2°structure. Accordingly, Guinn et al. propose that TSs often contain the native 2°structure with most of the tertiary contacts forming post-TS. Structural modeling indicates that this level of 2°struc-ture organizes the chain into the native fold before the TS and the rate-limiting step is the formation of a key set of tertiary contacts. Because the amide and hydrocarbon burial are preferentially buried pre-and post-TS, respectively, the authors suggest that these two quantities along with total burial are natural reaction coordinates.The results by Guinn et al. emphasizing 2°structure over hydrophobicity (2) evoke a comparison with the long-standing debate on the determinants of protein stability. Pauling and others stressed the importance of hydrogen bonds (3), but Kauzmann later argued that the hydrophobic effect is the dominant factor (4). However, more recent work has revisited this conclusion (5). Analogously, early kinetics models focused on the role of 2°structure (6), whereas later work emphasized hydrophobic collapse and the possibility that 2°-structure formation is driven by the collapse process (7).The analysis by Guinn et al. indicates that amide surface is preferentially buried in the TS.The native level of 2°structure in the TS proposed by Guinn et al. (2) is higher than indicated by most other experimental methods (Table 1). The predominant method for studying the TS has been mutational ϕ analysis. This method has supported a variety of folding models, but it generally indicates that multiple 2°structural elements can be absent in the TS (8-10). The newer Ψ analysis method, which uses bi-histidine metal ionbinding sites to explicitly identify ...

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Diffusion–collision model for protein folding

Cited by 188 publications

References 24 publications

Funnels, pathways, and the energy landscape of protein folding: A synthesis

Funnels, pathways, and the energy landscape of protein folding: A synthesis

Protein Folding Problem

Revealing what gets buried first in protein folding

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