title: A two-state model for the dynamics of the pyrophosphate ion release in bacterial RNA polymerase.
abstract: The dynamics of the PPi release during the transcription elongation of bacterial RNA polymerase and its effects on the Trigger Loop (TL) opening motion are still elusive. Here, we built a Markov State Model (MSM) from extensive all-atom molecular dynamics (MD) simulations to investigate the mechanism of the PPi release. Our MSM has identified a simple two-state mechanism for the PPi release instead of a more complex four-state mechanism observed in RNA polymerase II (Pol II). We observed that the PPi release in bacterial RNA polymerase occurs at sub-microsecond timescale, which is ∼3-fold faster than that in Pol II. After escaping from the active site, the (Mg-PPi)(2-) group passes through a single elongated metastable region where several positively charged residues on the secondary channel provide favorable interactions. Surprisingly, we found that the PPi release is not coupled with the TL unfolding but correlates tightly with the side-chain rotation of the TL residue R1239. Our work sheds light on the dynamics underlying the transcription elongation of the bacterial RNA polymerase.
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Lin-Tai
authors.initials: LT
authors.lastname: Da
authors.forename: Fátima
authors.initials: F
authors.lastname: Pardo Avila
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Xuhui
authors.initials: X
authors.lastname: Huang
mesh_terms: D020816:Amino Acid Motifs; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry*; D011756:Diphosphates / Q000737:chemistry*; D007477:Ions; D008390:Markov Chains; D056004:Molecular Dynamics Simulation; D011336:Probability; D017510:Protein Folding; D012313:RNA / Q000737:chemistry; D013824:Thermus / Q000201:enzymology; D013997:Time Factors
chemical_list: D011756:Diphosphates; D007477:Ions; D012313:RNA; D004247:DNA; D012321:DNA-Directed RNA Polymerases