Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides
Polymerases select nucleotides according to a template before incorporating them for chemical synthesis during gene replication or transcription. Efficient selection to achieve sufficiently high fidelity and speed is essential for polymerase function. Due to multiple kinetic steps detected in a poly...
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| Format: | Article |
| Language: | English |
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De Gruyter
2014-01-01
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| Series: | Computational and Mathematical Biophysics |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/mlbmb-2014-0010 |
| _version_ | 1818728286746836992 |
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| author | Yu Jin |
| author_facet | Yu Jin |
| author_sort | Yu Jin |
| collection | DOAJ |
| description | Polymerases select nucleotides according to a template before incorporating them for chemical synthesis during gene replication or transcription. Efficient selection to achieve sufficiently high fidelity and speed is essential for polymerase function. Due to multiple kinetic steps detected in a polymerase elongation cycle, there exist multiple selection checkpoints to allow different strategies of fidelity control. In our current work, we examined step-by-step selections in an elongation cycle that have conformational transition rates tuned one at a time, with a controlled differentiation free energy between the right and wrong nucleotides at each checkpoint. The elongation is sustained at non-equilibrium steady state with constant free energy input and heat dissipation. It is found that a selection checkpoint in the later stage of a reaction path has less capability for error reduction. Hence, early selection is essential to achieve an efficient fidelity control. In particular, for an intermediate state, the selection through the forward transition inhibition has the same capacity for error reduction as the selection through the backward rejection. As with respect to the elongation speed, an initial screening is indispensible for maintaining high speed, as the wrong nucleotides can be removed quickly and replaced by the right ones at the entry. Overall, the elongation error rate can be repeatedly reduced through multiple selection checkpoints. This study provides a theoretical framework to guide more detailed structural dynamics studies, and to support rational redesign of related enzymes and devices. |
| first_indexed | 2024-12-17T22:27:35Z |
| format | Article |
| id | doaj.art-725c8e4735544d3883f87c8cec21a71e |
| institution | Directory Open Access Journal |
| issn | 2544-7297 |
| language | English |
| last_indexed | 2024-12-17T22:27:35Z |
| publishDate | 2014-01-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Computational and Mathematical Biophysics |
| spelling | doaj.art-725c8e4735544d3883f87c8cec21a71e2022-12-21T21:30:19ZengDe GruyterComputational and Mathematical Biophysics2544-72972014-01-012114116010.2478/mlbmb-2014-0010mlbmb-2014-0010Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotidesYu Jin0Beijing Computational Science Research Center, No. 3 He-Qing Road, Hai-Dian District,Beijing, P. R. ChinaPolymerases select nucleotides according to a template before incorporating them for chemical synthesis during gene replication or transcription. Efficient selection to achieve sufficiently high fidelity and speed is essential for polymerase function. Due to multiple kinetic steps detected in a polymerase elongation cycle, there exist multiple selection checkpoints to allow different strategies of fidelity control. In our current work, we examined step-by-step selections in an elongation cycle that have conformational transition rates tuned one at a time, with a controlled differentiation free energy between the right and wrong nucleotides at each checkpoint. The elongation is sustained at non-equilibrium steady state with constant free energy input and heat dissipation. It is found that a selection checkpoint in the later stage of a reaction path has less capability for error reduction. Hence, early selection is essential to achieve an efficient fidelity control. In particular, for an intermediate state, the selection through the forward transition inhibition has the same capacity for error reduction as the selection through the backward rejection. As with respect to the elongation speed, an initial screening is indispensible for maintaining high speed, as the wrong nucleotides can be removed quickly and replaced by the right ones at the entry. Overall, the elongation error rate can be repeatedly reduced through multiple selection checkpoints. This study provides a theoretical framework to guide more detailed structural dynamics studies, and to support rational redesign of related enzymes and devices.https://doi.org/10.2478/mlbmb-2014-0010polymerase elongationnucleotide selectionfidelitynon-equilibrium steady state |
| spellingShingle | Yu Jin Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides Computational and Mathematical Biophysics polymerase elongation nucleotide selection fidelity non-equilibrium steady state |
| title | Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides |
| title_full | Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides |
| title_fullStr | Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides |
| title_full_unstemmed | Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides |
| title_short | Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides |
| title_sort | efficient fidelity control by stepwise nucleotide selection in polymerase elongation abstract polymerases select nucleotides |
| topic | polymerase elongation nucleotide selection fidelity non-equilibrium steady state |
| url | https://doi.org/10.2478/mlbmb-2014-0010 |
| work_keys_str_mv | AT yujin efficientfidelitycontrolbystepwisenucleotideselectioninpolymeraseelongationabstractpolymerasesselectnucleotides |