Wetting the lock and key enthalpically favours polyelectrolyte binding

Jeamet, Emeric; Septavaux, Jean; Héloin, Alexandre; Donnier-Maréchal, Marion; Dumartin, Melissa; Ourri, Benjamin; Mandal, Pradeep K.; Huc, Ivan; Bignon, Emmanuelle; Dumont, Élise; Morell, Christophe; Francoïa, Jean-Patrick; Perret, Florent; Vial, Laurent; Leclaire, Julien

doi:10.1039/c8sc02966k

Cited by 13 publications

(22 citation statements)

References 38 publications

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“…This value is lowered by 3.0 kcal.mol −1 in the experiments and 5.3 kcal.mol −1 in MD simulations compared to the first association, due to a smaller accessible protein surface area (see ITC results). This confirms the performance of MM-PBSA to evaluate the binding free energies [59][60][61][62] , and validates in turn our computational approach. For both associations, the additive decomposition per type of residues reveals that the Cyt c-sclx 8 binding cannot be viewed as a lysine-only problem.…”

Section: Resultssupporting

confidence: 84%

Capturing the Supramolecular Association of Calixarenes onto Proteins Relying on Molecular Dynamics Simulations: The Case of Cytochrome C

Bartocci¹,

Szczepaniak²,

Jiang³

et al. 2020

Preprint

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Here, we propose a molecular dynamics investigation of the supramolecular association of sulfonatedcalix-[8]-arenes to cytochrome c. The binding sites prone to interactions with sulfonated calixarenescan be identified without prior knowledge of the X-ray structure, and the binding free energiesestimated by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) post-analysis arefound to be in neat agreement with the isothermal titration calorimetry (ITC) measurements The per-residuedecomposition reveals the detailed picture of this electrostatically-driven association and notably therole of the arginine R13 as a bridge residue between the two main anchoring sites. In addition,the analysis of the residue behavior by means of a supervised machine learning protocol unveils the formation of an hydrogen bond network far from the binding sites, increasing the rigidity of theprotein.

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Section: Resultssupporting

confidence: 84%

Capturing the Supramolecular Association of Calixarenes onto Proteins Relying on Molecular Dynamics Simulations: The Case of Cytochrome C

Bartocci¹,

Szczepaniak²,

Jiang³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…This value is lowered by 3.0 kcal.mol −1 in the experiments and 5.3 kcal.mol −1 in MD simulations compared to the first association, probably because of a smaller accessible protein surface area 25 . Our results confirm the performance of MM-PBSA to evaluate the binding free energies [66][67][68][69] , and validate in turn our computational approach for the characterization of the protein-molecular glue association.…”

Section: Resultssupporting

confidence: 80%

Molecular Dynamics Approach for Capturing Calixarene–Protein Interactions: The Case of Cytochrome C

et al. 2020

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Functionalized supramolecular cages are of growing importance in biology and biochemistry. They have recently been proposed as efficient auxiliaries to obtain high-resolution cocrystallized proteins. Here, we propose a molecular dynamics investigation of the supramolecular association of sulfonated calix-[8]-arenes to cytochrome c starting from initially distant protein and ligands. We characterize two main binding sites for the sulfonated calixarene on the cytochrome c surface which are in perfect agreement with the previous experiments with regard to the structure (comparison with the X-ray structure PDB 6GD8) and the binding free energies (comparison between the molecular mechanics Poisson-Boltzmann surface 1 area (MM-PBSA) analysis and the isothermal titration calorimetry (ITC) measurements).The per-residue decomposition of the interaction energies reveals the detailed picture of this electrostatically-driven association and notably the role of the arginine R13 as a bridging residue between the two main anchoring sites. In addition, the analysis of the residue behavior by means of a supervised machine learning protocol unveils the formation of an hydrogen bond network far from the binding sites, increasing the rigidity of the protein. This study paves the way towards an automated procedure to predict the supramolecular protein-cages association, with the possibility of a computational screening of new promising derivatives for controlled protein assembly and protein surface recognition processes.

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“…In the former complex, formed with longer diamines, less intimate contact between charged groups enables to preserve a monolayer of water between the polar regions of the binding partners, which eventually is enthalpically more favorable. This deviation from the lock and key paradigm, well known in molecular biology and especially in protein binding [59] was termed by us “the hydrophilic effect” [60] . It shed some new light on how binding enthalpy can be optimized in the framework of molecular recognition in water.…”

Section: Synthesis‐structure‐function Relationshipsmentioning

confidence: 99%

“…This deviation from the lock and key paradigm, well known in molecular biology and especially in protein binding [59] was termed by us "the hydrophilic effect". [60] It shed some new light on how binding enthalpy can be optimized in the framework of molecular recognition in water. We are currently exploring the subtle features of host-guest binding entropy in aqueous solution with an aim of providing the community with similar guidelines.…”

Section: Template-free Stereochemical Information Encoding On Dyn[n]a...mentioning

confidence: 99%

Dyn[n]arenes: Versatile Platforms To Study the Interplay between Covalent and Noncovalent Bonds

2022

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Dyn[n]arenes are the strict polydisulfide‐based analogues of pillar[n]arenes. Although less famous than their static homologues, these dynamic cavitands possess unique (stereo)chemical features. The disulfide bridge between monomeric units not only provides these architectures with constitutional lability but is also an additional stereogenic element. As a result, the covalent assembling process can be guided by supramolecular interactions with or without a targeted partner, enabling to decipher supramolecular at work from the synthetic stage. Not only can the size and functions be chosen on demand, but the stereochemical features can be precisely controlled by careful choice on the assembling conditions. Eventually, deciphering the interactions at work during self‐assembly opens the way toward innovative applications such as biomolecules sensing. This account describes the synergistic interplay between covalent and noncovalent bounds found in dyn[n]arenes.

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Wetting the lock and key enthalpically favours polyelectrolyte binding

Abstract: We explored the factors governing the association between a polyanionic dyn[4]arene and a series of α-ω-alkyldiammonium ions of increasing chain length in water.

Cited by 13 publications

References 38 publications

Capturing the Supramolecular Association of Calixarenes onto Proteins Relying on Molecular Dynamics Simulations: The Case of Cytochrome C

Capturing the Supramolecular Association of Calixarenes onto Proteins Relying on Molecular Dynamics Simulations: The Case of Cytochrome C

Molecular Dynamics Approach for Capturing Calixarene–Protein Interactions: The Case of Cytochrome C

Dyn[n]arenes: Versatile Platforms To Study the Interplay between Covalent and Noncovalent Bonds

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