On the transferability of fractional contributions to the hydration free energy of amino acids

Campanera, Josep M.; Barril, Xavier; Luque, F. Javier

doi:10.1007/s00214-013-1343-y

Cited by 3 publications

(2 citation statements)

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“…This energetic behavior is common for proteins and peptides that balance solvation and internal stability. 109 Two final important things to remark, first, the arrow of the total stability free energy (DG total ) displays the direction of its highest variability, which points in the direction that permits the visual separation of the level of aggregation from dimers to octamers. And second, the compactness of the oligomer clusters in the biplot could also be a measure of the convergence of the present results.…”

Section: The Increase In Intermonomeric Vdw Interactions In the Oligo...mentioning

confidence: 99%

Energetic contributions of residues to the formation of early amyloid-β oligomers

Pouplana

Campanera

2015

Phys. Chem. Chem. Phys.

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Low-weight amyloid-β (Aβ) oligomers formed at early stages of oligomerization rather than fibril assemblies seem to be the toxic components that drive neurodegeneration in Alzheimer's disease. Unfortunately, detailed knowledge of the structure of these early oligomers at the residue level is not yet available. In this study, we performed all-atom explicit solvent molecular dynamics simulations to examine the oligomerization process of Aβ10-35 monomers when forming dimers, trimers, tetramers and octamers, with four independent simulations of a total simulated time of 3 μs for each oligomer system. The decomposition of the stability free energy by MM-GBSA methodology allowed us to unravel the network of energetic interactions that stabilize such oligomers. The contribution of the intermonomeric van der Waals term is the most significant energy feature of the oligomerization process, consistent with the so-called hydrophobic effect. Furthermore, the decomposition of the stability free energy into residues and residue-pairwise terms revealed that it is mainly apolar interactions between the three specific hydrophobic fragments 31-35 (C-terminal region), 17-20 (central hydrophobic core) and 12-14 (N-terminal region) that are responsible for such a favourable effect. The conformation in which the hydrophobic cthr-chc interaction is oriented perpendicularly is particularly important. We propose three other model substructures that favour the oligomerization process and can thus be considered as molecular targets for future inhibitors. Understanding Aβ oligomerization at the residue level could lead to more efficient design of inhibitors of this process.

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Section: The Increase In Intermonomeric Vdw Interactions In the Oligo...mentioning

confidence: 99%

Energetic contributions of residues to the formation of early amyloid-β oligomers

Pouplana

Campanera

2015

Phys. Chem. Chem. Phys.

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“…Let us note that the choice of N -acetyl- l -amino acid amides in this study enables a direct comparison with the experimental results reported by Fauchère and Pliska because their experimental lipophilicity scaled was determined using these model systems in their study. The partition coefficients P N and P I were determined from theoretical computations using the B3LYP/6-31G(d) version of the quantum-mechanical IEFPCM-MST continuum solvation method, which relies on the integral equation formalism (IEF) of the polarizable continuum model (PCM). , Following our previous study of the hydration free energy of the natural amino acids, the backbone-dependent conformational library compiled by Drunback and coworkers − () was used to extract the conformational preferences of residues, which defined the ensemble of structures used to estimate the log D p H values from IEFPCM-MST calculations in n -octanol and water. (See the SI for a detailed description of the computational methods.…”

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confidence: 99%

Development of a Structure-Based, pH-Dependent Lipophilicity Scale of Amino Acids from Continuum Solvation Calculations

Zamora

Campanera

Luque

2019

J. Phys. Chem. Lett.

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From canonical to unique: extension of a lipophilicity scale of amino acids to non-standard residues

Viayna,

Matamoros,

Blázquez-Ruano

et al. 2024

Explor Drug Sci

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Aim:The lipophilicity of amino acids plays a crucial role in delineating their physicochemical properties, offering insights into solubility, binding affinity, and bioavailability, properties that are a cornerstone for the use of peptides as therapeutic agents. In this study, we employ the integral equation formalism polarizable continuum model/Miertus-Scrocco-Tomasi (IEFPCM/MST) implicit solvation model to compute the n-octanol/water partition coefficient, serving as a lipophilic descriptor for non-standard amino acids. This approach allows us to expand upon our prior scale developed for canonical amino acids. Methods: Using the IEFPCM/MST implicit solvation model, we extended our previous work on the hydrophobicity scale of amino acids. To this end, we employed two structural models, Model 1 and 2, differentiated solely by their C-terminal capping groups using an N-or O-methyl substituent, respectively. Results: Our findings revealed substantial similarities between the models, validating the lipophilicity values for the non-standard side chains. Differences were observed in fewer cases, indicating an effect of the capping group on the side chain hydrophobicity. This effect is expected as one model contains a hydrogen bond donor (Model 1) while the other one uses a hydrogen bond acceptor (Model 2). Conclusions: Overall, both models exhibit good correlations with the experimental values, with Model 1 showing lower statistical errors. In addition, our predictions were able to correctly predict the experimental hydrophobicity change due to the number of acetylated lysines in peptide pairs determined by HPLC, suggesting that our scale can be employed for proteomics studies that include post-translational modifications beyond acetylation.

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On the transferability of fractional contributions to the hydration free energy of amino acids

Cited by 3 publications

References 73 publications

Energetic contributions of residues to the formation of early amyloid-β oligomers

Energetic contributions of residues to the formation of early amyloid-β oligomers

Development of a Structure-Based, pH-Dependent Lipophilicity Scale of Amino Acids from Continuum Solvation Calculations

From canonical to unique: extension of a lipophilicity scale of amino acids to non-standard residues

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