| Recent experiments uncovered a mutational pathway between two proteins, GA and GB, along which a single mutation causes a switch in fold, between a 3alpha and a mixed alpha/beta fold. I will present preliminary results from an implicit solvent all-atom study of how the conformational preferences vary along this mutational pathway. I will also present a study of fold switching in the minimalistic HP model on a square lattice. For this study, we created a comprehensive structure/sequence database for chains with up to 30 beads, which exceeds previous work by five units. Single-mutation-induced fold switching turns out to be quite common in this model. The switches define a fold network, whose topology we investigate. A search restricted to paths with the minimum number of mutations fails to correctly identify 40% of single-mutation-linked fold pairs that we observe. The thermodynamic stability is correlated with mutational stability and is, on average, markedly reduced at the observed fold switches. |
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