Analyzing the effect of homogeneous frustration in protein folding

Contessoto, Vinícius G.; Lima, Debora T.; Oliveira, Ronaldo Junio de; Bruni, Aline Thais; Chahine, Jorge; Leite, Vitor Barbanti Pereira

doi:10.1002/prot.24309

Cited by 34 publications

(56 citation statements)

References 63 publications

(163 reference statements)

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“…In the structure-based model (SBM), the residues of a protein are represented by individual beads centered in C a position (18,(48)(49)(50)(51). The energy of the protein is given by a Hamiltonian equation in which only the native interactions based on its native topology are taken into account (48).…”

Section: Constant-ph Molecular Dynamics Simulationsmentioning

confidence: 99%

Effects of pH and Salt Concentration on Stability of a Protein G Variant Using Coarse-Grained Models

Oliveira

Contessoto

Silva

et al. 2018

Biophysical Journal

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The importance of charge-charge interactions in the thermal stability of proteins is widely known. pH and ionic strength play a crucial role in these electrostatic interactions, as well as in the arrangement of ionizable residues in each protein-folding stage. In this study, two coarse-grained models were used to evaluate the effect of pH and salt concentration on the thermal stability of a protein G variant (1PGB-QDD), which was chosen due to the quantity of experimental data exploring these effects on its stability. One of these coarse-grained models, the TKSA, calculates the electrostatic free energy of the protein in the native state via the Tanford-Kirkwood approach for each residue. The other one, CpHMD-SBM, uses a Coulomb screening potential in addition to the structure-based model C. Both models simulate the system in constant pH. The comparison between the experimental stability analysis and the computational results obtained by these simple models showed a good agreement. Through the TKSA method, the role of each charged residue in the protein's thermal stability was inferred. Using CpHMD-SBM, it was possible to evaluate salt and pH effects throughout the folding process. Finally, the computational pK values were calculated by both methods and presented a good level of agreement with the experiments. This study provides, to our knowledge, new information and a comprehensive description of the electrostatic contribution to protein G stability.

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Section: Constant-ph Molecular Dynamics Simulationsmentioning

confidence: 99%

Effects of pH and Salt Concentration on Stability of a Protein G Variant Using Coarse-Grained Models

Oliveira

Contessoto

Silva

et al. 2018

Biophysical Journal

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“…Very recently, Contessoto etc. studied the interplay between energetic and topological frustrations for a set of 19 proteins of different folding motifs and sizes, also using a Gaussian potential function for energetic frustrations [42]. Taken together, these researches highlighted the overall effects of frustrations on protein folding, including the formation of on-pathway intermediates, acceleration of initial folding, etc.…”

Section: Introductionmentioning

confidence: 99%

Energetic Frustrations in Protein Folding at Residue Resolution: A Homologous Simulation Study of Im9 Proteins

Sun

Ming

2014

PLoS ONE

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Energetic frustration is becoming an important topic for understanding the mechanisms of protein folding, which is a long-standing big biological problem usually investigated by the free energy landscape theory. Despite the significant advances in probing the effects of folding frustrations on the overall features of protein folding pathways and folding intermediates, detailed characterizations of folding frustrations at an atomic or residue level are still lacking. In addition, how and to what extent folding frustrations interact with protein topology in determining folding mechanisms remains unclear. In this paper, we tried to understand energetic frustrations in the context of protein topology structures or native-contact networks by comparing the energetic frustrations of five homologous Im9 alpha-helix proteins that share very similar topology structures but have a single hydrophilic-to-hydrophobic mutual mutation. The folding simulations were performed using a coarse-grained Gō-like model, while non-native hydrophobic interactions were introduced as energetic frustrations using a Lennard-Jones potential function. Energetic frustrations were then examined at residue level based on φ-value analyses of the transition state ensemble structures and mapped back to native-contact networks. Our calculations show that energetic frustrations have highly heterogeneous influences on the folding of the four helices of the examined structures depending on the local environment of the frustration centers. Also, the closer the introduced frustration is to the center of the native-contact network, the larger the changes in the protein folding. Our findings add a new dimension to the understanding of protein folding the topology determination in that energetic frustrations works closely with native-contact networks to affect the protein folding.

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“…The sequence of specific R groups determines the minimum-free-energy folding of the protein (Muff and Caflisch, 2009; Schuetz et al, 2010; Liwo et al, 2011; Contessoto et al, 2013; Marinelli, 2013). Thus, the prescribed sequencing blossoms into deeper layers of meaning (Abel, 2000, 2011c, 2012a,b; Kellera, 2011; D'Onofrio et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Redundancy of the genetic code enables translational pausing

D'Onofrio

Abel²

2014

Front. Genet.

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The codon redundancy (“degeneracy”) found in protein-coding regions of mRNA also prescribes Translational Pausing (TP). When coupled with the appropriate interpreters, multiple meanings and functions are programmed into the same sequence of configurable switch-settings. This additional layer of Ontological Prescriptive Information (PIo) purposely slows or speeds up the translation-decoding process within the ribosome. Variable translation rates help prescribe functional folding of the nascent protein. Redundancy of the codon to amino acid mapping, therefore, is anything but superfluous or degenerate. Redundancy programming allows for simultaneous dual prescriptions of TP and amino acid assignments without cross-talk. This allows both functions to be coincident and realizable. We will demonstrate that the TP schema is a bona fide rule-based code, conforming to logical code-like properties. Second, we will demonstrate that this TP code is programmed into the supposedly degenerate redundancy of the codon table. We will show that algorithmic processes play a dominant role in the realization of this multi-dimensional code.

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Analyzing the effect of homogeneous frustration in protein folding

Cited by 34 publications

References 63 publications

Effects of pH and Salt Concentration on Stability of a Protein G Variant Using Coarse-Grained Models

Effects of pH and Salt Concentration on Stability of a Protein G Variant Using Coarse-Grained Models

Energetic Frustrations in Protein Folding at Residue Resolution: A Homologous Simulation Study of Im9 Proteins

Redundancy of the genetic code enables translational pausing

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