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Record W4392288047 · doi:10.5530/pj.2024.16.8

Predictive Simulation and Functional Insights of Serotonin Transporter: Ligand Interactions Explored through Database Analysis

2024· article· en· W4392288047 on OpenAlex
Irzan Nurman, Ninik Mudjihartini, Nurhadi Ibrahim, Linda Erlina, Fadilah Fadilah, Muchtaruddin Mansyur

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenuePharmacognosy Journal · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsInnovation Cluster (Canada)
Fundersnot available
KeywordsSerotonin transporterSerotonin Plasma Membrane Transport ProteinsTransporterParoxetineLigand (biochemistry)ChemistrySerotoninIn silicoHydrogen bondStereochemistryBiochemistryReceptorMolecule

Abstract

fetched live from OpenAlex

Through its ability to facilitate the absorption of serotonin into presynaptic neurons, the serotonin transporter, also known as SERT, an essential component in the control of neurotransmission. To discover SERT possible therapeutic application, it is essential to have a solid understanding of its dynamic behavior, ligand interactions, and functional consequences. Within the scope of this investigation, the predictive simulations is crucial to investigate the complexities of SERT to gain a fresh understanding of its operation. We use the 6AWN model to describe the sequence and simulate the behavior of SERT in silico. Within this simulation, we anticipate the conformational changes of SERT and its reaction to ligand binding with paroxetine, cholesterol, dodecyl-beta-D-maltose (DDM), and sodium hydrogen ion. We discover critical residues that are crucial in the interaction between ligands and proteins. They have paroxetine binding to I.172, I.172, Y.176, and F.341 are examples of hydrophobic interactions. Example of hydrogen bonds include A.96 and pi-stacking: F.341. The blockage of the serotonin transporter is the principal mechanism of action that paroxetine has. Cholesterol interacts with SERT W.500, W.500, W.500, W.500, L.504, and A.507, and it also interacts with the outward-facing conformation of this transporter in two different ways. In general, cholesterol interacts with SERT and ligands to stabilize their optimal activity and structure. DDM contact with SERT is also a part of this interaction. R.104, D.328, E.494, Y.495, G.498, P.499, T.503, F.556, L.557, S.559, P.561, Y.579, G.582, T.583, and F.586 are the numbers that are currently in use. Within the context of glucosyl transfer processes, DDM has been utilized as an acceptor. And the interaction of Na with SERT S.263, which causes a change in the structure of SERT. Serotonin transporters are present in the environment.

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.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.266
Threshold uncertainty score0.399

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 communication0.0000.000
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 head0.036
GPT teacher head0.326
Teacher spread0.291 · 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