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author:

Li, Z. (Li, Z..) [1] | Song, G. (Song, G..) [2] | Zhu, J. (Zhu, J..) [3] | Mu, J. (Mu, J..) [4] | Sun, Y. (Sun, Y..) [5] | Hong, X. (Hong, X..) [6] (Scholars:洪晓昆) | Choi, T. (Choi, T..) [7] | Cui, X. (Cui, X..) [8] | Chen, H.-F. (Chen, H.-F..) [9]

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Abstract:

Excited-ground-state transition and strand slippage of RNA play key roles in transcription and translation of central dogma. Due to limitation of current experimental techniques, the dynamic structure ensembles of RNA remain inadequately understood. Molecular dynamics simulations offer a promising complementary approach, whose accuracy depends on the force field. Here, we develop the new version of RNA base-specific force field (BSFF2) to address underestimation of base pairing stability and artificial backbone conformations. Extensive evaluations on typical RNA systems have comprehensively confirmed the accuracy of BSFF2. Furthermore, BSFF2 demonstrates exceptional efficiency in de novo folding of tetraloops and reproducing base pair reshuffling transition between RNA excited and ground states. Then, we explored the RNA strand slippage mechanism with BSFF2. We conducted a comprehensive three-dimensional structural investigation into the strand slippage of the most complex r(G4C2)9 repeat element and presented the molecular details in the dynamic transition along with the underlying mechanism. Our results of capturing the strand slippage, excited-ground transition, de novo folding, and simulations for various typical RNA motifs indicate that BSFF2 should be one of valuable tools for dynamic conformation research and structure prediction of RNA, and a future contribution to RNA-targeted drug design as well as RNA therapy development. © 2024 American Chemical Society.

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  • [ 1 ] [Li Z.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 2 ] [Song G.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 3 ] [Zhu J.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 4 ] [Mu J.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 5 ] [Sun Y.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 6 ] [Hong X.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 7 ] [Hong X.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350116, China
  • [ 8 ] [Choi T.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 9 ] [Cui X.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  • [ 10 ] [Chen H.-F.]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China

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Journal of Chemical Theory and Computation

ISSN: 1549-9618

Year: 2024

Issue: 14

Volume: 20

Page: 6082-6097

5 . 7 0 0

JCR@2023

CAS Journal Grade:1

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count: 1

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 2

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