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Chin. Phys. B, 2016, Vol. 25(1): 018706    DOI: 10.1088/1674-1056/25/1/018706
Special Issue: TOPICAL REVIEW — 8th IUPAP International Conference on Biological Physics
TOPICAL REVIEW—8th IUPAP International Conference on Biological Physics Prev   Next  

Computational investigations on polymerase actions in gene transcription and replication: Combining physical modeling and atomistic simulations

Jin Yu(喻进)
Beijing Computational Science Research Center, Beijing 100094, China

Polymerases are protein enzymes that move along nucleic acid chains and catalyze template-based polymerization reactions during gene transcription and replication. The polymerases also substantially improve transcription or replication fidelity through the non-equilibrium enzymatic cycles. We briefly review computational efforts that have been made toward understanding mechano-chemical coupling and fidelity control mechanisms of the polymerase elongation. The polymerases are regarded as molecular information motors during the elongation process. It requires a full spectrum of computational approaches from multiple time and length scales to understand the full polymerase functional cycle. We stay away from quantum mechanics based approaches to the polymerase catalysis due to abundant former surveys, while addressing statistical physics modeling approaches along with all-atom molecular dynamics simulation studies. We organize this review around our own modeling and simulation practices on a single subunit T7 RNA polymerase, and summarize commensurate studies on structurally similar DNA polymerases as well. For multi-subunit RNA polymerases that have been actively studied in recent years, we leave systematical reviews of the simulation achievements to latest computational chemistry surveys, while covering only representative studies published very recently, including our own work modeling structure-based elongation kinetic of yeast RNA polymerase II. In the end, we briefly go through physical modeling on elongation pauses and backtracking activities of the multi-subunit RNAPs. We emphasize on the fluctuation and control mechanisms of the polymerase actions, highlight the non-equilibrium nature of the operation system, and try to build some perspectives toward understanding the polymerase impacts from the single molecule level to a genome-wide scale.

Keywords:  polymerase      molecular dynamics simulation      kinetic modeling      fidelity  
Received:  03 May 2015      Revised:  26 June 2015      Accepted manuscript online: 
PACS:  87.15.A- (Theory, modeling, and computer simulation)  
  87.15.ap (Molecular dynamics simulation)  
  87.15.kj (Protein-polynucleotide interactions)  
  87.15.rp (Polymerization)  

Project supported by the National Natural Science Foundation (Grant No. 11275022).

Corresponding Authors:  Jin Yu     E-mail:

Cite this article: 

Jin Yu(喻进) Computational investigations on polymerase actions in gene transcription and replication: Combining physical modeling and atomistic simulations 2016 Chin. Phys. B 25 018706

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