Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6.

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. As a critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high-throughput structure-based computational screening using ensemble docking for small-molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein.

Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6.

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. A critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies are in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high throughput structure-based computational screening using ensemble docking for small molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein.

GPRC6A is a Potential Therapeutic Target for Metformin Regulation of Glucose Homeostasis in Mice.

Understanding the mechanism of metformin actions in treating type 2 diabetes is limited by an incomplete knowledge of the specific protein targets mediating its metabolic effects. Metformin has structural similarities to L-Arginine (2-amino-5-guanidinopentanoic acid), which is a ligand for GPRC6A, a Family C G-protein coupled receptor that regulates energy metabolism. Ligand activation of GPRC6A results in lowering of blood glucose and other metabolic changes resembling the therapeutic effect of metformin.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, ) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing.