Biology subjects

Ali, M. C.

Publications and source records attributed to Ali, M. C..

3 recordsLinked to original sources

bioRxiv2026

Targeting PRMT5 Across Cancers and AI-Driven Discovery of Candidate Compounds

Protein arginine methyltransferase 5 (PRMT5) is a promising anticancer target, yet existing inhibitors shown limited clinical efficacy. Here, we paired multi-omics pan-cancer profiling with a machine learning virtual screening pipeline. Bioinformatics analyses with TIMER3, GEPIA2, UALCAN/CPTAC, the Human Protein Atlas, cBioPortal, STRING and Enrichr revealed widespread of PRMT5 mRNA expression, protein abundance, survival, genetic alteration, immune infiltration and co-expression networks with tumor-specific prognostic impact in GBM, LGG and KIRC. A deep neural network screened about 1.5 million PubChem compounds and deep neural network reached a ROC-AUC = 0.9857 and prioritized three candidates, CID 44345182, CID 2794188 and CID 44345334. Subsequent molecular docking against PRMT5 (PDB ID: 4X61), ADMET filtering and toxicity prediction, and 100 ns molecular dynamics (MD) simulations identified CID 44345182 as the potential hit, similar the docking scores of -9.8 compared with -9.2 kcal/mol for the reference ligand in binding affinity and trajectory stability. These findings clarify the context-dependent roles of PRMT5 and further experiment validations are needed to establish CID 44345182 as a promising candidate.

bioinformatics↗

bioRxiv2024

Proteostasis Associated Variants in HSPB5 Destabilize the αB-crystallin Domain

HSPB5 (B-crystallin) is an ATP-independent, stress-inducible chaperone protein that improves protein misfolding and degradation in proteotoxicity-related diseases, including several myopathies, neurodegenerative diseases, and cancers. Although single nucleotide polymorphism (SNP) reduces the overall activity of HSPB5, its dynamic behaviour remains unknown. To get molecular insights into the deleterious, pathogenic, and proteotoxicity-related mutations, this study investigates the potential deleterious SNPs associated with HSPB5. Notably, eleven computational tools identified D109H, R120G, and D140N as the most deleterious SNPs from a total of 313 missense SNPs. Interestingly, these three mutations are present in the core B-crystallin (B-c) domain. A molecular dynamics simulation for 500 ns was conducted to reveal these variants mechanistic insights. The mutant variants showed higher flexibility and significant conformational changes than the wild, which might be noteworthy to reduce these variants chaperoning activity. Also, this conformational change elucidated the loss of function mutations, which could alter these variants oligomeric properties. This study will help our understanding of the role and molecular mechanism of HSPB5 mutations in proteotoxicity vulnerable diseases.

bioinformatics↗

bioRxiv2020

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

Curcuma amada or Mango ginger, a member of the Zingiberaceae family, has been revealed as a beneficiary medicinal plant having diverse pharmacological activities against a wide range of diseases. Due to having neuromodulation properties of this plant, the present study characterized the secondary metabolites of Curcuma amada for their drug-likeness properties, identified potent hits by targeting Acetylcholinesterase (AChE) and revealed neuromodulatory potentiality by network pharmacology approaches. Here in silico ADMET analysis was performed for chemical profiling, and molecular docking and molecular dynamics simulations were used to hit selection and binding characterizations. Accordingly, ADMET prediction showed that around 87.59% of compounds processed drug-likeness activity, where four compounds have been screened out by molecular docking. Guided from induced-fit docking, molecular dynamics simulations revealed phytosterol and curcumin derivatives as the most favorable AChE inhibitors with the highest binding energy, as resulted from MM-PBSA analysis. Furthermore, all of the four hits were appeared to modulate several signaling molecules and intrinsic cellular pathways in network pharmacology analysis, which are associated with neuronal growth survival, inflammation, and immune response, supporting their capacity to revert the condition of neuro-pathobiology. Together, the present in silico based characterization and system pharmacology based findings demonstrate Curcuma amada, as a great source of neuromodulating compounds, which brings about new development for complementary and alternative medicine for the prevention and treatment of neurodegenerative disorders.

bioinformatics↗