Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition
RNA polymerase catalyzes transcription with a high fidelity. If DNA/RNA mismatch or DNA damage occurs downstream, a backtracked RNA polymerase can proofread this situation. However, the backtracked mechanism is still poorly understood. Here we have performed multiple explicit-solvent molecular dynam...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-11-01
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| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmolb.2015.00061/full |
| _version_ | 1811265783738662912 |
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| author | Haifeng eChen Haifeng eChen |
| author_facet | Haifeng eChen Haifeng eChen |
| author_sort | Haifeng eChen |
| collection | DOAJ |
| description | RNA polymerase catalyzes transcription with a high fidelity. If DNA/RNA mismatch or DNA damage occurs downstream, a backtracked RNA polymerase can proofread this situation. However, the backtracked mechanism is still poorly understood. Here we have performed multiple explicit-solvent molecular dynamics (MD) simulations on bound and apo DNA/RNA hybrid to study backtracked recognition. MD simulations at room temperature suggest that specific electrostatic interactions play key roles in the backtracked recognition between the polymerase and DNA/RNA hybrid. Kinetics analysis at high temperature shows that bound and apo DNA/RNA hybrid unfold via a two-state process. Both kinetics and free energy landscape analyses indicate that bound DNA/RNA hybrid folds in the order of DNA/RNA contracting, the tertiary folding and polymerase binding. The predicted Φ-values suggest that C7, G9, dC12, dC15 and dT16 are key bases for the backtracked recognition of DNA/RNA hybrid. The average RMSD values between the bound structures and the corresponding apo ones and Kolmogorov-Smirnov (KS) P test analyses indicate that the recognition between DNA/RNA hybrid and polymerase might follow an induced fit mechanism for DNA/RNA hybrid and conformation selection for polymerase. Furthermore, this method could be used to relative studies of specific recognition between nucleic acid and protein. |
| first_indexed | 2024-04-12T20:30:09Z |
| format | Article |
| id | doaj.art-191988ecf16e47e8bcf2f27836062fba |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-12T20:30:09Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-191988ecf16e47e8bcf2f27836062fba2022-12-22T03:17:46ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2015-11-01210.3389/fmolb.2015.00061166625Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked RecognitionHaifeng eChen0Haifeng eChen1Shanghai Jiaotong UniversityShanghai Center for Bioinformation TechnologyRNA polymerase catalyzes transcription with a high fidelity. If DNA/RNA mismatch or DNA damage occurs downstream, a backtracked RNA polymerase can proofread this situation. However, the backtracked mechanism is still poorly understood. Here we have performed multiple explicit-solvent molecular dynamics (MD) simulations on bound and apo DNA/RNA hybrid to study backtracked recognition. MD simulations at room temperature suggest that specific electrostatic interactions play key roles in the backtracked recognition between the polymerase and DNA/RNA hybrid. Kinetics analysis at high temperature shows that bound and apo DNA/RNA hybrid unfold via a two-state process. Both kinetics and free energy landscape analyses indicate that bound DNA/RNA hybrid folds in the order of DNA/RNA contracting, the tertiary folding and polymerase binding. The predicted Φ-values suggest that C7, G9, dC12, dC15 and dT16 are key bases for the backtracked recognition of DNA/RNA hybrid. The average RMSD values between the bound structures and the corresponding apo ones and Kolmogorov-Smirnov (KS) P test analyses indicate that the recognition between DNA/RNA hybrid and polymerase might follow an induced fit mechanism for DNA/RNA hybrid and conformation selection for polymerase. Furthermore, this method could be used to relative studies of specific recognition between nucleic acid and protein.http://journal.frontiersin.org/Journal/10.3389/fmolb.2015.00061/fullConformational selectionInduced fitBacktracked RNA polymeraseDNA/RNA hybridP test |
| spellingShingle | Haifeng eChen Haifeng eChen Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition Frontiers in Molecular Biosciences Conformational selection Induced fit Backtracked RNA polymerase DNA/RNA hybrid P test |
| title | Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition |
| title_full | Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition |
| title_fullStr | Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition |
| title_full_unstemmed | Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition |
| title_short | Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition |
| title_sort | conformational selection and induced fit for rna polymerase and rna dna hybrid backtracked recognition |
| topic | Conformational selection Induced fit Backtracked RNA polymerase DNA/RNA hybrid P test |
| url | http://journal.frontiersin.org/Journal/10.3389/fmolb.2015.00061/full |
| work_keys_str_mv | AT haifengechen conformationalselectionandinducedfitforrnapolymeraseandrnadnahybridbacktrackedrecognition AT haifengechen conformationalselectionandinducedfitforrnapolymeraseandrnadnahybridbacktrackedrecognition |