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Record W4413103698 · doi:10.1021/acs.jcim.5c00828

How Do Food Compounds Interact with Their Protein Targets? Alternative Modes for Protein Binding

2025· article· en· W4413103698 on OpenAlexaff
Mario Astigarraga, Verónica López-Alejandre, Andrés Sánchez-Ruiz, Gonzalo Colmenarejo

Bibliographic record

VenueJournal of Chemical Information and Modeling · 2025
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsArtificial Intelligence in Medicine (Canada)
FundersEuropean Regional Development FundMinisterio de Ciencia, Tecnología e Innovación Productiva
KeywordsFood proteinChemistryProtein–protein interactionComputational biologyFood scienceComputer scienceBiochemistryBiology

Abstract

fetched live from OpenAlex

A large body of research is oriented toward the determination of the mechanism of action of food compounds at the molecular level in order to rationalize the important role of these molecules in health and as a source of new drugs. In this work, we perform a systematic analysis of all the food-protein complexes at atomic resolution present in the Protein Data Bank. We analyze both the interaction types used in their binding as well as the functional groups involved in these; from the protein side, we also analyze the partner amino acid types and their interaction types, as well as the corresponding protein classes. For the analysis, food compounds are divided into a set of molecules derived from fatty lipids (FoodFL, which includes glycerolipids, glycerophospholipids, and fatty acyls) and the rest of the molecules (FoodnoFL), since these correspond to highly dissimilar chemical spaces. As a control, a set of drugs is used. From this analysis, it is found that the three compound sets establish protein-ligand complexes through alternative binding modes. Thus, although the most dominant interaction in the three sets is the hydrophobic one, each compound set displays some characteristic interaction types compared with the others. FoodnoFL compounds have a characteristically high content of hydrogen bonds, salt bridges, cation-π interactions, and metal coordinations, while FoodFL compounds have characteristically high hydrophobic interactions. In turn, drugs stem for their characteristically high π-π, cation-π, and halogen bond interactions. These differences result from differences in the types and relative abundances of functional groups, differential usage of interaction types by the same functional groups, and differential usage of interaction types by the partner amino acids. This new knowledge can be exploited in the design of new drugs inspired by food compounds.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.448
Threshold uncertainty score0.544

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.003
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.030
GPT teacher head0.291
Teacher spread0.261 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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