How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution

might usefully be decreased) that would be expected to contain examples that have much better properties than any observed thus far. This consequently requires careful choices of examples drawn from an extensive distribution (using active learning) for predictive modelling. For instance, a widespread view of a trade-off between catalytic activity and thermostability seems to follow directly from inadequate sampling. All of this has significant implications for the understanding, modelling, and optimisation of experiments in directed evolution and the biocatalysts they produce.