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Record W4386099731 · doi:10.21203/rs.3.rs-3272416/v1

An in-silico approach of assessments of human serotonin transporter inhibitory potential of various flavonoids for anti-depressants: molecular docking, MM-GBSA, molecular dynamics simulation studies

2023· preprint· en· W4386099731 on OpenAlexaff
Sudhakar Nagarajan, Srikanth Jeyabalan, D. Sivaraman, Mahendran Sekar, Ling Shing Wong, B. Logeshwari, Chetan Ashok

Bibliographic record

VenueResearch Square · 2023
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsRoyal College of Physicians and Surgeons of Canada
FundersJSS College of Pharmacy
KeywordsIn silicoDocking (animal)Serotonin transporterChemistryPharmacologyNorepinephrine transporterReuptakeTricyclicTransporterSerotoninStereochemistryBiochemistryMedicineReceptorGene

Abstract

fetched live from OpenAlex

Abstract Depression is one of the typical CNS disorders. Millions of people suffer from depression, a chronic illness with economic consequences. Tricyclic antidepressants, selective dopamine reuptake inhibitors, selective norepinephrine reuptake inhibitors, and selective serotonin reuptake inhibitors are only few of the antidepressants that can used to treat depression. The main target of therapeutic activity is known to be the serotonin transporter (SERT) against depressants. In this article, various flavonoids were found with conditions of pharmacological activity and were designed by molecular docking, MM-GBSA and molecular dynamics (MD) Simulation studies for the treatment of depressants activity. The docking of ligands performed against depressant with protein of human serotonin transporter (SERT) PDB-ID:5I6X are performed by using Glide module, in silico ADMET screening by QikProp module, binding energy using Prime MMGB/SA module, MD simulation by Desmond module and atomic charges were derived by Jaguar module of Schrodinger suite 2021-1. Compounds with top binding affinity using extra precision in glide recorded as (-16.25) when compared to standard FDA approved drug Fluoxetine (-8.711) which were proposed for anti-depressant action. The residues PHE 335, TYR 95, ALA 96, PHE 341, VAL 501, TRP 103, TYR 175, ALA 169, GLY 338 of SERT Play a crucial role as binding pocket of ligands. The in-silico ADMET properties of the molecules were within the recommended values. The binding free energy was calculated using PRIME MM-GB/SA studies. Compound with top binding affinity of flavonoids was subjected to MD simulation at 100 ns to study the dynamic behavior of protein–ligand complex.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.117
GPT teacher head0.493
Teacher spread0.377 · 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 source (direct Gemma or distilled Codex), 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

Citations2
Published2023
Admission routes1
Has abstractyes

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