> but they had enough effective (remotely) homologous sequences to predict coevolution-derived interresidue distances and contacts. Ah, I see what you're sayin

> but they had enough effective (remotely) homologous sequences to predict coevolution-derived interresidue distances and contacts. Ah, I see what you're saying a bit better. Makes more sense to how the the possible "design" space for novel proteins could be limited. Designing novel active sites could be especially tricky, more than it'd seem at first glance. A folded structure that'd effectively transfer electrons from one target species to another in a catalyzer protein could likely be outside the explored "vocabulary" of extant proteins as it'd require specialized pathways and precise positioning. Chlorophyll is pretty unchanged in evolution as I understand it.Thanks, interesting background! I'll keep an eye out for the de novo design algorithms.