Speaker
Description
While most folded proteins adopt a single, conformationally homogeneous native state, a small but growing class of proteins is known to reversibly switch between two structurally distinct folds. These fold transitions are typically triggered by changes in the local environment, such as binding to a partner molecule or variations in salt concentration or temperature, and often enable new, unrelated biological functions. Understanding the physical mechanisms underlying such fold switching remains a major challenge. We have developed a structure-based coarse-grained model capable of simulating both the thermodynamics and kinetics of fold switching. In this talk, I will discuss its application to both the engineered fold switch GA/GB, driven by point mutations, and the natural metamorphic protein XCL1, which switches folds upon dimerization. Using this model, we probe universal features of fold-switching mechanisms, examine how macromolecular crowding reshapes the free-energy landscape and alters relative fold populations, and characterize structural changes in the unfolded state under conditions favoring the different folds.
| Keyword-1 | Computational |
|---|---|
| Keyword-2 | Proteins |
| Keyword-3 | Fold switching |