Publications by authors named "Shahlo Solieva"
Human interleukin-2 (IL-2) is a crucial cytokine for T cell regulation, with therapeutic potential in cancer and autoimmune diseases. However, IL-2's pleiotropic effects across different immune cell types often lead to toxicity and limited efficacy. Previous efforts to enhance IL-2's therapeutic profile have focused on modifying its receptor binding sites.
View Article and Find Full Text PDFMonoclonal antibodies are an important class of biologics with over 160 Food and Drug Administration/European Union-approved drugs. A significant bottleneck to global accessibility of recombinant monoclonal antibodies stems from complexities related to their production, storage, and distribution. Recently, gene-encoded approaches such as mRNA, DNA, or viral delivery have gained popularity, but ensuring biologically relevant levels of antibody expression in the host remains a critical issue.
View Article and Find Full Text PDFArticle Synopsis
- Human interleukin-2 (IL-2) is essential for T cell regulation and has potential in treating cancer and autoimmune diseases, but its widespread effects can cause toxicity and limit effectiveness.
- This study explores the dynamics of IL-2 compared to engineered variants, "superkines" S15 and S1, which show enhanced signaling towards effector T cells, using NMR spectroscopy and molecular dynamics.
- The research identifies unique allosteric networks and distinct dynamic behaviors in the superkines, suggesting that altering IL-2's dynamics could lead to better therapeutic designs with improved targeting of immune cells.
Article Synopsis
- In genetic cardiomyopathies, similar mutations in the β-MHC protein can cause different heart diseases, such as hypertrophic cardiomyopathy (HCM) and left ventricular non-compaction (LVNC).
- Research on specific mutations (I467V and I467T) revealed that while both mutations have similar mechanical functions, they affect the SRX state of myosin differently, leading to distinct phenotypes.
- The HCM mutation leads to a "gain-of-function" effect by reducing the SRX state, while the LVNC mutation increases the SRX state and alters ADP release, resulting in unique contractile dysfunctions that could inform therapies for these conditions.
Cryptic pockets, or pockets absent in ligand-free, experimentally determined structures, hold great potential as drug targets. However, cryptic pocket openings are often beyond the reach of conventional biomolecular simulations because certain cryptic pocket openings involve slow motions. Here, we investigate whether AlphaFold can be used to accelerate cryptic pocket discovery either by generating structures with open pockets directly or generating structures with partially open pockets that can be used as starting points for simulations.
View Article and Find Full Text PDFThe polyextremophilic β-galactosidase enzyme of the haloarchaeon functions in extremely cold and hypersaline conditions. To better understand the basis of polyextremophilic activity, the enzyme was studied using steady-state kinetics and molecular dynamics at temperatures ranging from 10 °C to 50 °C and salt concentrations from 1 M to 4 M KCl. Kinetic analysis showed that while catalytic efficiency (/) improves with increasing temperature and salinity, is reduced with decreasing temperatures and increasing salinity, consistent with improved substrate binding at low temperatures.
View Article and Find Full Text PDF