Influence of the chain stiffness on the thermodynamics of a Gō-type model for protein folding

Prieto, Lidia; Rey, Antonio

doi:10.1063/1.2727465

Cited by 12 publications

(32 citation statements)

References 53 publications

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“…First, increasing R C/D increases contact strength. As seen in other simplified models [60], when each contact is stronger, a smaller number of contacts is required (lower Q) to provide an equal amount of stabilizing energy. The second contributing factor is the change in side chain entropy.…”

Section: Resultsmentioning

confidence: 96%

An all‐atom structure‐based potential for proteins: Bridging minimal models with all‐atom empirical forcefields

et al. 2008

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Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Gō) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a Cα structure-based model and an all-atom empirical forcefield. Key findings include 1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature 2) folding mechanisms are robust to variations of the energetic parameters 3) protein folding free energy barriers can be manipulated through parametric modifications 4) the global folding mechanisms in a Cα model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model 5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Since this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function.

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Section: Resultsmentioning

confidence: 96%

An all‐atom structure‐based potential for proteins: Bridging minimal models with all‐atom empirical forcefields

et al. 2008

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“…The other model used in this work is a modification of this potential in which the local interactions are defined in a non-topology-based manner, by including a generic local interactions potential. This creates a more flexible protein backbone, something that can induce a folding process with different characteristics for individual chains, 17 increasing the possibilities for a high population of intermediate states.…”

Section: The Model and Simulation Methodsmentioning

confidence: 99%

“…17,51 This extension has been made in the same way as Yang et al 50 did to consider interchain interactions, and also used by other groups. 49 The functional form of this potential is…”

Section: A Symmetrized 100% Gō-type Potentialmentioning

confidence: 99%

“…To better consider the effect of a possibly different folding barrier, or the presence of thermodynamic intermediates along the folding process, one should normally consider a different protein, with a different folded structure, which could therefore influence the full process in a different way. In a computer simulation model, however, one can keep the same structure and modify the interaction characteristics to define a different folding transition, 17,51 which can therefore change the aggregation possibilities. From our experience with coarse-grained topology-based models, in this part of the study we have modified the local interactions, maintaining the long range interactions, which are defined in the same way as in the pure topology-based potential.…”

Section: B Generic Local Interactions Potentialmentioning

confidence: 99%

“…This type of interaction, initially developed by Gō and collaborators in lattice models, 1-3 defines minimally frustrated systems for the energy of the folded state, 4 and have been extensively used in protein folding studies. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] These works have proven that topology-based potentials are useful to study protein folding pathways 3,10,12,14,19 as well as folding intermediates. 7,8 The success of these potentials can be explained by the fact that folding seems to be a minimally frustrated process for many proteins, but not all ͑for example, proteins that fold via intermediates that are not na-tivelike͒.…”

Section: Introductionmentioning

confidence: 99%

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Topology-based potentials and the study of the competition between protein folding and aggregation

Prieto

Rey

2009

The Journal of Chemical Physics

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Topology-based or Go-type potentials have been shown to be very useful in the understanding of the relations between the structure of the native state of a protein and some of its folding characteristics. A different question is whether they can also make such a contribution when the aggregation process of misfolded or partially folded structures is under study. In this work, in spite of the obvious trend of these simulation models toward the native state, we show that there are some aspects about aggregation that can be addressed by topology-based potentials: the role of the thermodynamic characteristics of the transition on preventing the aggregation process, or the larger propensity of highly symmetric protein structures to form domain swapped dimers. In a second part of this work, we use the possibilities of computer simulation as a design of numerical experiments to analyze the fundamental role of intermediate states in the aggregation process of globular proteins.

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Topology‐based models and NMR structures in protein folding simulations

2008

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Topology-based interaction potentials are simplified models that use the native contacts in the folded structure of a protein to define an energetically unfrustrated folding funnel. They have been widely used to analyze the folding transition and pathways of different proteins through computer simulations. Obviously, they need a reliable, experimentally determined folded structure to define the model interactions. In structures elucidated through NMR spectroscopy, a complex treatment of the raw experimental data usually provides a series of models, a set of different conformations compatible with the available experimental data. Here, we use an efficient coarse-grained simulation technique to independently consider the contact maps from every different NMR model in a protein whose structure has been resolved by the use of NMR spectroscopy. For lambda-Cro repressor, a homodimeric protein, we have analyzed its folding characteristics with a topology-based model. We have focused on the competition between the folding of the individual chains and their binding to form the final quaternary structure. From 20 different NMR models, we find a predominant three-state folding behavior, in agreement with experimental data on the folding pathway for this protein. Individual NMR models, however, show distinct characteristics, which are analyzed both at the level of the interplay between tertiary/quaternary structure formation and also regarding the thermal stability of the tertiary structure of every individual chain.

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Influence of the chain stiffness on the thermodynamics of a Gō-type model for protein folding

Cited by 12 publications

References 53 publications

An all‐atom structure‐based potential for proteins: Bridging minimal models with all‐atom empirical forcefields

An all‐atom structure‐based potential for proteins: Bridging minimal models with all‐atom empirical forcefields

Topology-based potentials and the study of the competition between protein folding and aggregation

Topology‐based models and NMR structures in protein folding simulations

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