TY - JOUR T1 - A Two-State Model for the Dynamics of the Pyrophosphate Ion Release in Bacterial RNA Polymerase A1 - Da, Lin-Tai A1 - Pardo Avila, Fátima A1 - Wang, Dong A1 - Huang, Xuhui Y1 - 2013/04/04 N2 - Author Summary Pyrophosphate ion (PPi) release is a critical step in the nucleotide addition cycle of transcription elongation. Despite extensive experimental studies, the kinetic mechanism of the PPi release in bacterial RNA polymerases (RNAP) still remains largely a mystery. As a cellular machine, RNAP contains more than 3000 residues, and thus it is challenging for all-atom molecular dynamics (MD) simulations to directly capture the process of the PPi release. In this study, we have simulated the dynamics of the PPi release at microsecond timescale using the Markov State Models (MSMs) built from extensive MD simulations in explicit solvent. MSM is a powerful kinetic network model and can predict long timescale dynamics from many short MD simulations. Our results suggest a simple two-state model for the PPi release in RNAP, which sharply contrasts with the more complex four-state hopping model in the yeast RNA polymerase (Pol II). We also observe a 3-fold faster dynamics for the PPi release in RNAP compared to Pol II, consistent with the faster transcription rate in the bacterial systems. Our results greatly improve our understanding of the PPi release, and also provide predictions to guide future experimental tests. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 9 IS - 4 UR - https://doi.org/10.1371/journal.pcbi.1003020 SP - e1003020 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1003020 ER -