• Filip Fratev posted an update in the hub Micar 21 4 years, 6 months ago

    New upcoming paper! The longest MD simulations on a nuclear receptor reported to date have been performed by Micar21 scientific team. These results revealed transition paths of the significant for the estrogen receptor function helix 12


    Nuclear receptors (NR) dynamics has been extensively studied. However, the transition path of helix 12 (H12) from an extended/unfolded form to an agonist and/or an antagonist conformation and the exchange pathway between these states is still unknown. Moreover, the presence of an extended NR H12 position, seen in some X-ray data, is…[Read more]

  • Molecular basis of inactive B-RAF(WT) and B-RAF(V600E) ligand inhibition, selectivity and conformational stability: an in silico study.

    The B-RAF kinase plays an important role both in tumor induction and maintenance in several cancers. The molecular basis of the inactive B-RAF(WT) and B-RAF(V600E) inhibition and selectivity of a series of inhibitors was examined with a combination of molecular dynamics (MD), free energy MM-PBSA and local-binding energy (LBE) approaches. The…[Read more]

  • Structural insight into the UNC-45-myosin complex.

    The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45-myosin complex using various in silico methods. Initially, the human UNC-45B…[Read more]

  • Discovery of a novel selective PPARγ ligand with partial agonist binding properties by integrated in silico/in vitro work flow.

    Full agonists to the peroxisome proliferator-activated receptor (PPAR)γ, such as Rosiglitazone, have been associated with a series of undesired side effects, such as weight gain, fluid retention, cardiac hypertrophy, and hepatotoxicity. Nevertheless, PPARγ is involved in the expression of genes that control glucose and lipid metabolism and is an i…[Read more]

  • Combination of genetic screening and molecular dynamics as a useful tool for identification of disease-related mutations: ZASP PDZ domain G54S mutation case.

    Cypher/ZASP (LDB3 gene) is known to interact with a network of proteins. It binds to α-actinin and the calcium voltage channels (LTCC) via its PDZ domain. Here we report the identification of a highly conserved ZASP G54S mutation classified as a variant of unknown significance in a sample of an adult with hypertrophic cardiomyopathy (HCM). The…[Read more]