THEORETICAL INVESTIGATIONS ON ELUCIDATING FUNDAMENTAL MECHANISMS OF CATALYSIS AND DYNAMICS INVOLVED IN TRANSCRIPTION BY RNA POLYMERASE.

RNA polymerase is the enzyme that synthesizes RNA during the transcription process. To understand its mechanism, structural studies have provided us pictures of the series of steps necessary to add a new nucleotide to the nascent RNA chain, the steps altogether known as the nucleotide addition cycle (NAC). However, these static snapshots do not provide dynamic information of these processes involved in NAC, such as the conformational changes of the protein and the atomistic details of the catalysis. Computational studies have made efforts to fill these knowledge gaps. In this review, we provide examples of different computational approaches that have improved our understanding of the transcription elongation process for RNA polymerase, such as normal mode analysis, molecular dynamic (MD) simulations, Markov state models (MSMs). We also point out some unsolved questions that could be addressed using computational tools in the future. The dynamics of the different steps in the transcription elongation cycle (EC) of RNA polymerase remain elusive. Here we show how computational tools, such as Normal Mode Analysis, QM/MM and Markov State Models, have improved our understanding of the EC. We also indicate how computational tools can be used to address other unsolved questions of the EC. [ABSTRACT FROM AUTHOR]