Hypertrophic cardiomyopathy (HCM) is a genetic condition of the heart that is commonly associated with mutations of sarcomeric proteins such as MYH7. Currently available therapies are largely palliative and do not offer cure-focused treatment. In this work, we utilize a computational approach combining molecular docking, Density Functional Theory (DFT), and Molecular Dynamics (MD) simulations to search for therapeutic compounds interacting with the MYH7 protein. Predicted models of MYH7 by Alpha Fold provided strong prediction reliability since 91.4% of residues were in the favored Ramachandran region. Out of multiple bioactive candidates screened, thymoquinone showed the most negative free energy of binding (-6.7 kcal/mol) to MYH7. Pharmacophore modeling along with ADMET analysis also validated its druglike nature and declared safety. Analyzing electronic properties showed that thymoquinone possesses a low HOMO-LUMO band gap (~5.67 eV), thus showcasing strong bioreactivity and stability. These results provide a direction for the intervention of MYH7 protein dysfunction. Such progress would aim at changing the treatments from palliative strategies to curative approach which is particularly essential to mitigate the risk of sudden cardiac death, especially in children. However further in vitro and in vivo studies are required to validate the safety and efficiency of the thymoquinone.

Background. Streptococcus pneumoniae is a major human pathogen responsible for serious infections such as pneumonia. Despite extensive research, many proteins in S. pneumoniae, including hypothetical proteins, remain uncharacterized, limiting the understanding of the bacterium's pathogenic mechanisms. Methods. This study utilizes in silico tools to characterize the hypothetical protein AZJ53_10480 from S. pneumoniae. Sequence alignment and phylogenetic analysis were conducted using BLASTp and ClustalW, while PSIPRED and I-TASSER predicted the protein’s secondary and tertiary structures. Molecular docking studies were performed with AutoDock Vina to assess potential interactions with the antiviral drug sofosbuvir Results. The in silico analysis revealed that the hypothetical protein AZJ53_10480 shares structural and functional similarities with viral capsid proteins of the hepatitis C virus. The protein was found to have a mixed localization, suggesting potential multifunctionality within the bacterial cell. Molecular docking studies indicated a strong binding affinity between AZJ53_10480 and sofosbuvir, suggesting that this protein could be a potential target for therapeutic intervention. Conclusion. This study highlights structural properties and functional roles of hypothetical protein AZJ53_10480 in S. pneumoniae of . The findings suggest that AZJ53_10480 may play a role in the pathogenicity of this bacterium and could serve as a novel target for therapeutic development. Further experimental studies are needed to validate these findings and explore the protein's potential as a drug target. Highlights In silico analysis reveals structural similarities between the hypothetical protein AZJ53_10480 and viral capsid proteins. Docking studies suggest AZJ53_10480 as a potential target for antiviral drugs like sofosbuvir. The study provides new insights into the possible pathogenic role of hypothetical proteins in Streptococcus pneumoniae.

Vibrio fluvialis is an emerging foodborne pathogen causing gastroenteritis and extraintestinal infections, representing a significant public health concern due to rising antimicrobial resistance and the absence of an approved vaccine. This study aimed to design a multi-epitope subunit vaccine against V. fluvialis using immunoinformatics and a standard multi-epitope vaccine design pipeline. Two surface-exposed immunogenic membrane proteins, ATP-dependent zinc metalloprotease FtsH and lytic murein transglycosylase F, were selected as antigenic targets. Ten epitopes, including four MHC class I, four MHC class II, and two B-cell epitopes, were predicted and assembled into a 246 amino acid vaccine construct. The construct showed an antigenicity score of 0.8610. Population coverage analysis indicated that these epitopes could potentially cover 99.97% of the global population. The vaccine exhibited favorable physicochemical properties, with an instability index of 33.18 and a GRAVY score of − 0.282, suggesting stability and hydrophilicity. The tertiary structure was modeled using AlphaFold3 and docked with Toll-like receptor 2, yielding a docking score of − 270.01. Molecular dynamics simulations for 100 ns suggested stability of the vaccine–TLR2 complex. Codon optimization indicated high expression potential in Escherichia coli, with a CAI value of 0.95. Overall, the vaccine showed strong in silico immunogenic potential and requires further experimental validation through in vitro and in vivo studies.

Neurosyphilis, a severe neurological complication of syphilitic infection caused by the gram-negative spirochete Treponema pallidum poses significant challenges in treatment due to its irregular physiology and lack of efficacy in present therapeutic strategies. Here, we report a new approach to developing drug treatment that targets the enzyme phosphoglycerate kinase (PGK), an essential component of the T. pallidum glycolytic pathway. Therefore, a ligand was designed involving common neuroprotectant elements reported from literature by a computational drug design method, to increase their binding energy with lower toxicity. The calculated binding affinity of the designed ligand with PGK was analyzed by molecular docking to be − 116.68 kcal/mol. Also, interaction analysis predicted that there are 5 hydrophobic bonds and 3 hydrogen bonds present between the docked complex. Afterward, in-silico ADMET studies were conducted for the designed ligand that determined a strong pharmacological profile with good absorption, zero violation of Lipinski’s rule, and non-toxic properties. DFT analysis further optimized the ligand with a HOMO/LOMO gap value of 0.01421 kcal/mol indicating higher reactivity and enhanced electronic interactions, improving ligand efficiency. Moreover, pharmacophore modeling confirmed the reactive nature of the ligand. Furthermore, MD simulations showed stability in the overall structure. The output shows that our optimized ligand has statistically better binding affinity than the currently used drug penicillin, with improved pharmacokinetic profiles. This work demonstrates the importance of ligand design for the discovery of new drugs to treat neurosyphilis.