In silico chemical profiling and identification of neuromodulators from Curcuma amada targeting acetylcholinesterase

Ali, Md. Chayan; Munni, Yeasmin Akter; Das, Rahul; Akter, Nasrin; Das, Kantu; Mitra, Sarmistha; Hannan, Md. Abdul; Dash, Raju

doi:10.1007/s13721-021-00334-2

Cited by 2 publications

(1 citation statement)

References 112 publications

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“…MD simulation was conducted using YASARA (YASARA Biosciences GmBH, Vienna, Austria) dynamics software, hydrogen bond network optimization 96 , 98 , 99 , 102 , 103 , and AMBER14 to apply force fields 100 , 101 . A simulation cell (Cubic box) was prepared in a periodic boundary condition and extended on each side such that it was 10 Å larger than the selected protein.…”

Section: Methodsmentioning

confidence: 99%

Dynamic insights into the effects of nonsynonymous polymorphisms (nsSNPs) on loss of TREM2 function

Dash

Munni

Mitra

et al. 2022

Sci Rep

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Single nucleotide variations in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with many neurodegenerative diseases, including Nasu-Hakola disease (NHD), frontotemporal dementia (FTD), and late-onset Alzheimer's disease because they disrupt ligand binding to the extracellular domain of TREM2. However, the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) in TREM2 on disease progression remain unknown. In this study, we identified several high-risk nsSNPs in the TREM2 gene using various deleterious SNP predicting algorithms and analyzed their destabilizing effects on the ligand recognizing region of the TREM2 immunoglobulin (Ig) domain by molecular dynamics (MD) simulation. Cumulative prediction by all tools employed suggested the three most deleterious nsSNPs involved in loss of TREM2 function are rs549402254 (W50S), rs749358844 (R52C), and rs1409131974 (D104G). MD simulation showed that these three variants cause substantial structural alterations and conformational remodeling of the apical loops of the TREM2 Ig domain, which is responsible for ligand recognition. Detailed analysis revealed that these variants substantially increased distances between apical loops and induced conformation remodeling by changing inter-loop nonbonded contacts. Moreover, all nsSNPs changed the electrostatic potentials near the putative ligand-interacting region (PLIR), which suggested they might reduce specificity or loss of binding affinity for TREM2 ligands. Overall, this study identifies three potential high-risk nsSNPs in the TREM2 gene. We propose further studies on the molecular mechanisms responsible for loss of TREM2 function and the associations between TREM2 nsSNPs and neurodegenerative diseases.

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Section: Methodsmentioning

confidence: 99%

Dynamic insights into the effects of nonsynonymous polymorphisms (nsSNPs) on loss of TREM2 function

Dash

Munni

Mitra

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

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Structure-based virtual screening of Trachyspermum ammi metabolites targeting acetylcholinesterase for Alzheimer’s disease treatment

Musa,

Islam,

Billah

et al. 2024

PLoS ONE

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In recent decades, Alzheimer’s disease (AD) has garnered significant attention due to its rapid global prevalence. The cholinergic hypothesis posits that the degradation of acetylcholine by acetylcholinesterase (AChE) contributes to AD development. Despite existing anti-AChE drugs, their adverse side effects necessitate new agents. This study analyzed 150 bioactive phytochemicals from Trachyspermum ammi using structure-based drug design and various in-silico tools to identify potent anti-AChE compounds. Compounds were screened for drug-likeness (QEDw ≥50%) and bioavailability (≥55%) and underwent toxicity profiling via the ProTox-II server. Selected compounds were prepared for molecular docking with the human AChE protein as the receptor. Viridifloral, 2-Methyl-3-glucosyloxy-5-isopropyl phenol, Alpha-Curcumene, and Sterol emerged as top candidates with high AChE affinity. These results were validated by molecular dynamics simulations, confirming stable interactions. The hit compounds were further evaluated for drug-likeness using Lipinski’s rule and ADMET properties, confirming favorable pharmacokinetic profiles. DFT optimization analyzed frontier molecular orbitals and electrostatic potential, demonstrating favorable chemical reactivity and stability. This study suggests that these identified compounds could be novel nature-derived AChE inhibitors, potentially contributing to AD treatment. However, further in-vitro and in-vivo studies are necessary to confirm their efficacy in biological systems. Future research will focus on developing these compounds into safe and effective drugs to combat Alzheimer’s disease.

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In silico chemical profiling and identification of neuromodulators from Curcuma amada targeting acetylcholinesterase

Cited by 2 publications

References 112 publications

Dynamic insights into the effects of nonsynonymous polymorphisms (nsSNPs) on loss of TREM2 function

Dynamic insights into the effects of nonsynonymous polymorphisms (nsSNPs) on loss of TREM2 function

Structure-based virtual screening of Trachyspermum ammi metabolites targeting acetylcholinesterase for Alzheimer’s disease treatment

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