Killer yeast, like K1 of the species Saccharomyces cerevisiae , is a pore-forming toxin that can cause commercial problems due to its ability to kill desirable strains of yeast. These toxins remain poorly understood, yet they hold promise as potential solutions to the growing threat of fungal diseases. A key step in improving our knowledge is understanding how they bind to cellular components. K1 is one of the most extensively studied killer toxins, but its binding process is still not fully characterized. This work focuses on the interaction between K1 and its anchor protein Kre1, which mediates cell attachment. Starting from structural models of K1 generated by collaborators, molecular dynamics (MD) simulations were performed, followed by clustering and docking with Kre1. Stability assessments were performed on further MD simulations of poses with favorable scores, the most stable complex was identified, and key residues of Kre1 involved in the binding were determined. These residues provide targets for experimental validation through mutagenesis. Such results would verify our computational predictions and clarify the molecular mechanism underlying K1 toxicity, informing the design of novel antifungals.
Kittan et al. (Sun,) studied this question.