, 2006; Sawaya and Kraut, 1997; determine one—determine health supplement 1), we anticipated the mutational landscape of DHFR for being constrained through the necessity to adopt these distinct conformations. What's more, prior get the job done had proposed DHFR is impacted by cellular constraints for example protein quality Management (Bershtein et al., 2013) plus the Create-up of the toxic metabolic intermediate (Schober et al., 2019). We as a result expected deep mutational scanning to reveal a very constrained mutational landscape for DHFR that could distinction with the mutational tolerance noticed in other methods.
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