, 2006; Sawaya and Kraut, 1997; determine one—determine dietary supplement one), we envisioned the mutational landscape of DHFR to generally be constrained because of the requirement to undertake these distinctive conformations. Moreover, prior get the job done experienced recommended DHFR is impacted by cellular constraints for example protein top quality Regulate (Bershtein et al., 2013) as well as Make-up of the toxic metabolic intermediate (Schober et al., 2019). We hence envisioned deep mutational scanning to reveal a hugely constrained mutational landscape for DHFR that will contrast Along with the mutational tolerance observed in other devices.

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