, 2006; Sawaya and Kraut, 1997; determine 1—figure supplement 1), we anticipated the mutational landscape of DHFR to get constrained because of the necessity to adopt these distinct conformations. Furthermore, prior do the job had advised DHFR is impacted by mobile constraints like protein excellent Regulate (Bershtein et al., 2013) as well as the Construct-up of the poisonous metabolic intermediate (Schober et al., 2019). We that's why envisioned deep mutational scanning to reveal a remarkably constrained mutational landscape for DHFR that might distinction Along with the mutational tolerance noticed in other systems.

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