Characterization of RNA polymerase II trigger loop mutations using molecular dynamics simulations and machine learning.

ABSTRACT: Catalysis and fidelity of multisubunit RNA polymerases rely on a highly conserved active site domain called the trigger loop (TL), which achieves roles in transcription through conformational changes and interaction with NTP substrates. The mutations of TL residues cause distinct effects on catalysis including hypo- and hyperactivity and altered fidelity. We applied molecular dynamics simulation (MD) and machine learning (ML) techniques to characterize TL mutations in the Saccharomyces cerevisiae RNA Polymerase II (Pol II) system. We did so to determine relationships between individual mutations and phenotypes and to associate phenotypes with MD simulated structural alterations. Using fitness values of mutants under various stress conditions, we modeled phenotypes along a spectrum of conti

SUBMITTER: Dutagaci B 

PROVIDER: S-EPMC10069792 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature