Application of a Distance-Dependent Sigmoidal Dielectric Constant to the REMC/SAAP3D Simulations of Chignolin, Trp-Cage, and the G10q Mutant

Iwaoka, Michio; Yoshida, Kōji; Shimosato, Taku

doi:10.1007/s10930-020-09936-7

Cited by 3 publications

(4 citation statements)

References 64 publications

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“…where D w is the dielectric constant of water, D p is the dielectric constant inside a protein, and s is the slope of the sigmoidal function. In practice, we used values of 78, 2 and 0.6 for D w , D p and s , respectively, as stated in ( Iwaoka et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

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A refined pH-dependent coarse-grained model for peptide structure prediction in aqueous solution

Tufféry

Derreumaux

2023

Front. Bioinform.

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Introduction: Peptides carry out diverse biological functions and the knowledge of the conformational ensemble of polypeptides in various experimental conditions is important for biological applications. All fast dedicated softwares perform well in aqueous solution at neutral pH.Methods: In this study, we go one step beyond by combining the Debye-Hückel formalism for charged-charged amino acid interactions and a coarse-grained potential of the amino acids to treat pH and salt variations.Results: Using the PEP-FOLD framework, we show that our approach performs as well as the machine-leaning AlphaFold2 and TrRosetta methods for 15 well-structured sequences, but shows significant improvement in structure prediction of six poly-charged amino acids and two sequences that have no homologous in the Protein Data Bank, expanding the range of possibilities for the understanding of peptide biological roles and the design of candidate therapeutic peptides.

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Section: Methodsmentioning

confidence: 99%

“…In practice, we used values of 78, 2 and 0.6 for D w , D p and s, respectively, as stated in (Iwaoka et al, 2020).…”

Section: Debye-hückel Charge Interactionsmentioning

confidence: 99%

A refined pH-dependent coarse-grained model for peptide structure prediction in aqueous solution

Tufféry

Derreumaux

2023

Front. Bioinform.

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“… where q i and q j correspond to the charge of particles i and j , j > i + 1, respectively, r ij is the distance between the particles, l DH is the Debye length that depends of the ionic strength of the solvent, ϵ ( r ij ) is the dielectric constant that depends on the distance between the charges: where D w is the dielectric constant of water, D p is the dielectric constant inside a protein, s is the slope of the sigmoidal function. In practice, we use values of 78, 2 and 0.6 for D w , D p and s , respectively, as stated in [30]…”

Section: Methodsmentioning

confidence: 99%

“…where D w is the dielectric constant of water, D p is the dielectric constant inside a protein, s is the slope of the sigmoidal function. In practice, we use values of 78, 2 and 0.6 for D w , D p and s, respectively, as stated in [30] Since the sOPEP representation does not include all-atom side chains, but charges associated with particles of heterogeneous sizes, it is necessary to shift the energy curve to have energy values compatible with those of the Mie formulation. For each pair of particle, we shift the distance using:…”

Section: Debye-hückel Charge Interactionsmentioning

confidence: 99%

A refined pH-dependent coarse-grained model for peptide structure prediction in aqueous solution

Tufféry

Derreumaux

2022

Preprint

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Peptides carry out diverse biological functions and the knowledge of the conformational ensemble of polypeptides in various experimental conditions is important for biological applications. All fast dedicated softwares perform well in aqueous solution at neutral pH. In this study, we go one step beyond by combining the Debye-Hueckel formalism for charged-charged amino acid interactions and a coarse-grained potential of the amino acids to treat pH and salt variations. Using the PEP-FOLD framework, we show that our approach performs as well as the machine-leaning AlphaFold2 and TrRosetta methods for 15 well-structured sequences, but shows significant improvement in structure prediction of six poly-charged amino acids and two sequences that have no homologous in the Protein Data Bank, expanding the range of possibilities for the understanding of peptide biological roles and the design of candidate therapeutic peptides.

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Antioxidant Activity of a Selenopeptide Modelling the Thioredoxin Reductase Active Site is Enhanced by NH···Se Hydrogen Bond in the Mixed Selenosulfide Intermediate

Iwaoka

Oba

Matsumura

et al. 2022

CCB

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Background: Thioredoxin reductase (TrxR), one of the representative selenoenzymes, is an important antioxidant enzyme suppressing oxidative stress in living organisms. At the active site of human TrxR, the presence of a Sec•••His•••Glu catalytic triad was previously suggested. Method. In this study, a short selenopeptide mimicking this plausible triad, i.e., H-CUGHGE-OH (1), was designed, synthesized, and evaluated for the TrxR-like catalytic activity. Method: In this study, a short selenopeptide mimicking this plausible triad, i.e., H-CUGHGE-OH (1), was designed, synthesized, and evaluated for the TrxR-like catalytic activity Results: The molecular simulation in advance by REMC/SAAP3D predicted the preferential formation of Sec•••His•••Glu hydrogen bonding networks in the aqueous solution. Indeed, a significant antioxidant activity was observed for 1 in the activity assay using NADPH as a reductant and H2O2 as a substrate. Tracking the reaction between 1 and GSH by 77Se NMR revealed a reductive cleavage of the selenosulfide (Se-S) bond to generate the diselenide species. The observation suggested that in the transiently formed mixed Se-S intermediate, the NH•••Se hydrogen bond between the Sec and His residues leads a nucleophilic attack of the second thiol molecule not to the intrinsically more electrophilic Se atom but to the less electrophilic S atom of the Se-S bond. Ab initio calculations for the complex between MeSeSMe and an imidazolium ion at the MP2/6-31++G(d,p) level demonstrated that NH•••Se and NH•••S hydrogen bonds are equally favorable as the interaction modes. Thus, importance of the relative spatial arrangement of the Se-S bond with respect to the imidazole ring was suggested for the exertion of the TrxR-like catalytic activity. Conclusion: The proposed umpolung effect of NH•••Se hydrogen bond on the reactivity of a Se-S bond will be a useful tool for developing efficient TrxR models with high redox catalytic activity.

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Application of a Distance-Dependent Sigmoidal Dielectric Constant to the REMC/SAAP3D Simulations of Chignolin, Trp-Cage, and the G10q Mutant

Cited by 3 publications

References 64 publications

A refined pH-dependent coarse-grained model for peptide structure prediction in aqueous solution

A refined pH-dependent coarse-grained model for peptide structure prediction in aqueous solution

A refined pH-dependent coarse-grained model for peptide structure prediction in aqueous solution

Antioxidant Activity of a Selenopeptide Modelling the Thioredoxin Reductase Active Site is Enhanced by NH···Se Hydrogen Bond in the Mixed Selenosulfide Intermediate

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