ArticlePloS one2024
Exploring the most promising anti - Depressant drug targeting Microtubule Affinity Receptor Kinase 4 involved in Alzheimer's Disease through molecular docking and molecular dynamics simulation.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's Disease (AD) is the prevailing type of neurodegenerative illness, characterised by the accumulation of amyloid beta plaques. The symptoms associated with AD are memory loss, emotional variability, and a decline in cognitive functioning. To date, the pharmaceuticals currently accessible in the marketplace are limited to symptom management. According to several research, antidepressants have demonstrated potential efficacy in the management of AD. In this particular investigation, a total of 24 anti-depressant medications were selected as ligands, while the Microtubule Affinity Receptor Kinase 4 (MARK4) protein was chosen as the focal point of our study. The selection of MARK4 was based on its known involvement in the advancement of AD and other types of malignancies, rendering it a highly prospective target for therapeutic interventions. The initial step involved doing ADMET analysis, which was subsequently followed by molecular docking of 24 drugs. This was succeeded by molecular dynamics simulation and molecular mechanics generalised Born surface area (MMGBSA) calculations. Upon conducting molecular docking experiments, it has been determined that the binding affinities observed fall within the range of -5.5 kcal/mol to -9.0 kcal/mol. In this study, we selected six anti-depressant compounds (CID ID - 4184, 2771, 4205, 5533, 4543, and 2160) based on their binding affinities, which were determined to be -9.0, -8.7, -8.4, -8.3, -8.2, and -8.2, respectively. Molecular dynamics simulations were conducted for all six drugs, with donepezil serving as the control drug. Various analyses were performed, including basic analysis and post-trajectory analysis such as free energy landscape (FEL), polarizable continuum model (PCM), and MMGBSA calculations. Based on the findings from molecular dynamics simulations and the MMGBSA analysis, it can be inferred that citalopram and mirtazapine exhibit considerable potential as anti-depressant agents. Consequently, these compounds warrant further investigation through in vitro and in vivo investigations in the context of treating AD.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.