Biology subjects

Al-Amin, R. A.

Publications and source records attributed to Al-Amin, R. A..

4 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↗

bioRxiv2022

Magnetic Bead Based Proximity Extension Assay for Sensitive Protein and Extracellular Vesicles Detection

During the early stages of disease development, protein biomarkers can leak into the blood creating opportunities for early diagnosis of disease with minimally invasive sampling. These proteins biomarkers however are often masked by the presence of more abundant functional blood proteins, making specific detection a challenge with most current immunoassays. We we report on the development of a magnetic bead based solid-phase PEA (SP-PEA) for sensitive detection of proteins in plasma and serum samples. Antibody functionalized magnetic beads are used to capture the target of interest. Following capture, non-specifically bound proteins are washed off before PEA probes are added for detection of the bound proteins. Compared to hoogenous PEA, SP-PEA admits the use of larger sample volumes to increase available target molecules, higher concentration of detection reagents for more efficient formation of detection complexes and washes for removal of nonspecific background. We compared SP-PEA to solution phase PEA for the detection of cytokines: interlukin-6, interlukin-2, interlukin-4, interlukin-10 and Tumor Necrosis Factor-alpha, and we demonstrated an increased sensitivity by 15 to 60 fold in buffer and chicken serum. We further expanded SP-PEA to detect extracellular vesicles (EVs) through combinations of proteins on the surface of specific EV populations.

biochemistry↗

bioRxiv2022

Sensitive protein detection using site-specifically oligonucleotide-conjugated nanobodies

High-quality affinity probes are critical for sensitive and specific protein detection, in particular for detection of protein biomarkers at early phases of disease development. Proximity extension assays (PEA) have been used for high-throughput multiplexed protein detection of up to a few thousand different proteins in one or a few microliters of plasma. Clonal affinity reagents can offer advantages over the commonly used polyclonal antibodies (pAbs) in terms of reproducibility and standardization of such assays. Here we explore nanobodies (Nb) as an alternative to pAbs as affinity reagents for PEA. We describe an efficient site-specific approach for preparing high-quality oligo-conjugated Nb probes via enzyme coupling using Sortase A (SrtA). The procedure allows convenient removal of unconjugated affinity reagents after conjugation. The purified high-grade Nb probes were used in PEA and the reactions provided an efficient means to select optimal pairs of binding reagents from a group of affinity reagents. We demonstrate that Nb-based PEA (nano-PEA) for interleukin-6 (IL6) detection can augment assay performance, compared to the use of pAb probes. We identify and validate Nb combinations capable of binding in pairs without competition for IL6 antigen detection by PEA.

bioengineering↗

bioRxiv2017

A myopic perspective on the future of protein diagnostics

Plasma proteome analyses of the future promise invaluable insights into states of health, not only by measuring proteins whose role it is to ensure blood homeostasis, but increasingly also as a window into the health of practically any tissue in the body via so-called leakage protein biomarkers. Realizing more of this vast potential will require progress along many lines. Here we discuss the main ones, such as optimal selection of target proteins, affinity reagents, immunoassay formats, samples, and applications, with a view from ongoing work in our laboratory.

biochemistry↗