Structural Insights and Inhibitor Identification Against Mitogen-Activated Protein Kinase Kinase 7 (MAP2K7) Obtained in Microgravity Environment

Mitogen-activated protein kinase kinase 7 (MAP2K7) plays a central role in the c-Jun N-terminal kinase (JNK) signaling pathway, governing stress and inflammatory responses. It is a promising target for drug discovery in severe conditions such as arthritis, hepatoma, and cardiac hypertrophy. However, due to the poor structural resolution, the challenge of developing MAP2K7 inhibitors with specificity against other kinases remains significant. Proteins crystallize under microgravity in a space environment yield  a high-resolution structure and help in the drug discovery process. In the present study, we have devel- oped an automated approach to expedite the screening of chemical compounds utilizing the AutoDock Vina software. This approach was further used to identify potential inhibitors against the MAP2K7 pro- tein crystallized in a microgravity environment. More than 5200 compounds were obtained from the Zinc20 database for virtual screening against this protein, out of which 5 candidates were selected for fur- ther screening. Furthermore, molecular dynamics simulations highlighted the protein’s flexibility, with significant fluctuations mainly observed in the Gly-rich loop region. These findings provide valuable insights into the structural attributes of MAP2K7 and lay the groundwork for the development of spe- cific inhibitors against this protein. Crystals yielding superior reflections, unattainable on Earth, can be acquired in space, thereby enhancing their utility in structure-based drug design.