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Biology subjects

Garcia, A. M.

Publications and source records attributed to Garcia, A. M..

2 recordsLinked to original sources

Natural language signatures of psilocybin microdosing

Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics ("microdosing") on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose. Following a double-blind and placebo-controlled experimental design, we explored natural language as a resource to identify speech produced under the acute effects of psilocybin microdoses, focusing on variables known to be affected by higher doses: verbosity, semantic variability and sentiment scores. Except for semantic variability, these metrics presented significant differences between a typical active microdose of 0.5 g of psilocybin mushrooms and an inactive placebo condition. Moreover, machine learning classifiers trained using these metrics were capable of distinguishing between conditions with high accuracy (AUC{approx}0.8). Our results constitute first proof that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.

pharmacology and toxicology↗

Impact of protein conformational diversity on AlphaFold predictions

After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here we address the performance of AlphaFold2 predictions under this ensemble paradigm. Using a curated collection of apo-holo conformations, we found that AlphaFold2 predicts the holo form of a protein in 70% of the cases, being unable to reproduce the observed conformational diversity with an equivalent error than in the estimation of a single conformation. More importantly, we found that AlphaFold2s performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo-holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions.

bioinformatics↗