Allosteric regulatory control in dihydrofolate reductase is revealed by dynamic asymmetry.

ABSTRACT: We investigated the relationship between mutations and dynamics in Escherichia coli dihydrofolate reductase (DHFR) using computational methods. Our study focused on the M20 and FG loops, which are known to be functionally important and affected by mutations distal to the loops. We used molecular dynamics simulations and developed position-specific metrics, including the dynamic flexibility index (DFI) and dynamic coupling index (DCI), to analyze the dynamics of wild-type DHFR and compared our results with existing deep mutational scanning data. Our analysis showed a statistically significant association between DFI and mutational tolerance of the DHFR positions, indicating that DFI can predict functionally beneficial or detrimental substitutions. We also applied an asymmetric version of ou

SUBMITTER: Kazan IC 

PROVIDER: S-EPMC10357497 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature