Sujay Ray

1. Originally named ‘Zaire’ Ebola virus (EBOV), belonging to the Filoviridae family [1], the virus induces a severe haemorrhagic fever in both humans and nonhuman primates, presenting exceptional c...

The family of deubiquitinating enzymes is primarily involved in the removal of ubiquitin chains from specific target proteins. Among these proteins, ubiquitin-specific protease 12 (USP12 protein) has been identified as a key molecule in regulating cellular homeostasis, cancer progression, and immune regulation. This protein is reportedly associated with colorectal cancer, prostate cancer, and breast cancer, along with neurodegenerative disorders like Huntington's disease. The study of mutations in USP12 could be crucial for understanding its impact on cancer and neurodegeneration, making it a potential target for therapeutics against such diseases. Our study uses a sequence-based and a structure-based screening method to identify a mutation in USP12 having the most deleterious and destabilizing effect. The mutation Y49N was found to significantly alter structural and biological functions of USP12 protein while compromising its stability. A total of 5000 conformations were generated for wild-type and Y49N_USP12 structures through normal mode analysis and a comparative study was conducted. We evaluated parameters like RMSD and R_g values to study structural divergence and reduced compactness in mutant protein conformations. Analysis of RMSF values of mutant protein showed significant structural deviations hinting at its increased flexibility. Further, heavily modified surface charge distributions were found through electrostatic surface charge mapping and fluctuations in energetic distribution indicated conformational perturbation. Moreover, the study shows how Y49N mutation could induce a helix to coil conversion in the N-terminal region of mutant protein structures throughout 5000 cycles of simulation. Our work helps advance our understanding of USP12 and its clinical value which needs to be explored further.

Metastatic castration resistance prostate cancer (mCRPC) is the advanced state of prostate cancer where majority of patients succumb to ineffective treatment perspectives like androgen deprivation alongside salvage therapies. mCRPC is predominantly orchestrated by androgen receptor (AR)‐dependent gene expression. On the account of AR being a “potentially attractive immunological target”, an immunoinformatics pipeline was built to identify and screen mutation‐independent, broad MHC covering, potential antigenic, non‐allergenic, non‐toxic and soluble epitopes. The filtered epitopes required assembly into a unified construct with interconnecting linkers and adjuvant and further TLR3‐docking. We chose TLR3 because of its pro‐apoptotic activity in prostate cancer, to check active immune response by the vaccine. Our study was not confined to the use of a conventional adjuvant like human beta defensin‐3 but it extended to the scope of utilization of a protein‐based TLR3‐specific agonist as an adjuvant for assembling the second composite construct. Our path was guided by the discovery of TLR3‐specific agonist minibinder 8.6 (a small, hyperstable protein) by Adams et al. An extensively comparative molecular dynamics study of the free state and bound states of the two constructs unveiled a more stable interaction, complex stability and immune response attributing to the specificity of the minibinder‐based construct towards TLR3. Our work circumscribes a multi‐headed approach beginning with peptide subunit multi‐epitope vaccine construct design for mitigating mCRPC; secondarily, endorsing the advocacy of TLR3‐agonizing minibinders as vaccine adjuvants for enhanced immunity and finally posing a comparative framework of minibinder 8.6 over HBD3, as a more potential adjuvant, apprehending wet‐lab proof.

Nine homologous Cold Shock Proteins (Csps) have been recognized in the E.coli Cold Shock Domain gene family. These Csps function as RNA chaperones. This st

Providencia stuartii , the most prevalent strain in its genus, is a significant cause of a range of potentially fatal diseases involving urinary tract infections, lung diseases, and endocarditis, often exhibiting resistance to multiple antibiotics, necessitating alternative therapeutic approaches. Unlike previous efforts focused on known virulence factors, this study delves into the physicochemical and functional characterization of 72 essential hypothetical proteins (EsHPs) from the P. stuartii BE246 genome. Subcellular localization identified 47 cytoplasmic EsHPs as potential drug targets, with the remainder 25 identified as vaccine targets. Subtractive analysis uncovered 68 virulent proteins, 4 of which were nonhomologous to both host and gut microbiota proteomes. Among these, WP_145928235.1 (147 amino acids), a cytoplasmic EsHP, emerged as a novel drug target due to its homologous broad‐spectrum hit. WP_145928235.1 displayed an instability index (II) of 33.14, an aliphatic index of 92.79, and the GRAVY score was ‐0.065 (hydrophilic). Molecular dynamics simulation‐aided conformational study and secondary structure analysis highlighted the protein's flexibility and propensity to interact with inhibitors. Key residues in the 60–90 region, including Asn62, Gly75, Glu81, and Asp85, were critical for interactions and stability, with low frustration indicating residual conservancy. WP_145928235.1 presents a promising target for therapeutic intervention against multidrug‐resistant P. stuartii infections.