Refinement of the AMBER Force Field for Nucleic Acids: Improving the Description of α/γ Conformers

Pérez, Alberto; Marchán, Ivan; Svozil, Daniel; Šponer, Jiřı́; Cheatham, Thomas E.; Laughton, Charles A.; Orozco, Modesto

doi:10.1529/biophysj.106.097782

Cited by 2,038 publications

(2,329 citation statements)

References 62 publications

(86 reference statements)

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“…Mixed-sequence 25-bp DNA and RNA duplexes were simulated using the AMBER14 suite of programs (27,28) with the parm10 force field, which includes parmbsc0 and parmbsc0_chiOL3 refinements (29,30) for DNA and RNA, respectively. Spermine molecules were simulated using the general Amber force field (GAFF version 1.7).…”

Section: All-atom MD Simulationsmentioning

confidence: 99%

Spermine Condenses DNA, but Not RNA Duplexes

Katz

Tolokh

Pabit

et al. 2017

Biophysical Journal

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Interactions between the polyamine spermine and nucleic acids drive important cellular processes. Spermine condenses DNA and some RNAs, such as poly(rA):poly(rU). A large fraction of the spermine present in cells is bound to RNA but apparently does not condense it. Here, we study the effect of spermine binding to short duplex RNA and DNA, and compare our findings with predictions of molecular-dynamics simulations. When small numbers of spermine are introduced, RNA with a designed sequence containing a mixture of 14 GC pairs and 11 AU pairs resists condensation relative to DNA of an equivalent sequence or to 25 bp poly(rA):poly(rU) RNA. A comparison of wide-angle x-ray scattering profiles with simulation results suggests that spermine is sequestered deep within the major groove of mixed-sequence RNA. This prevents condensation by limiting opportunities to bridge to other molecules and stabilizes the RNA by locking it into a particular conformation. In contrast, for DNA, simulations suggest that spermine binds externally to the duplex, offering opportunities for intermolecular interaction. The goal of this study is to explain how RNA can remain soluble and available for interaction with other molecules in the cell despite the presence of spermine at concentrations high enough to precipitate DNA.

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Section: All-atom MD Simulationsmentioning

confidence: 99%

Spermine Condenses DNA, but Not RNA Duplexes

Katz

Tolokh

Pabit

et al. 2017

Biophysical Journal

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“…to test parmbsc0 parameters in MD simulations (94). This approach was validated in various MD simulations of nucleic acids (95,96).…”

Section: Unfolding With Steered Molecular Dynamicsmentioning

confidence: 99%

Mechanical Unfolding of the Beet Western Yellow Virus −1 Frameshift Signal

et al. 2011

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“…In fact, there is a general consensus that the presence of the 2'OH drives the puckering preferences of the sugar from south (S, C2'endo) to north (N, C3'endo) conformations, which is known to drive a global conformational change from the B-to the A-form. 7 However, our understanding of the connection between the rotational state of the C2'-O2' bond and the local and global conformation of the RNA is still rather limited. In the A-form (sugar in north), the …”

Section: Introductionmentioning

confidence: 99%

Small Details Matter: The 2′-Hydroxyl as a Conformational Switch in RNA

et al. 2016

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While DNA is mostly a primary carrier of genetic information and displays a regular duplex structure, RNA can form very complicated and conserved 3D structures displaying a large variety of functions, such as being an intermediary carrier of the genetic information, translating such information into the protein machinery of the cell, or even acting as a chemical catalyst. At the base of such functional diversity is the subtle balance between different backbone, nucleobase, and ribose conformations, finely regulated by the combination of hydrogen bonds and stacking interactions. Although an apparently simple chemical modification, the presence of the 2'OH in RNA has a profound effect in the ribonucleotide conformational balance, adding an extra layer of complexity to the interactions network in RNA. In the present work, we have combined database analysis with extensive molecular dynamics, quantum mechanics, and hybrid QM/MM simulations to provide direct evidence on the dramatic impact of the 2'OH conformation on sugar puckering. Calculations provide evidence that proteins can modulate the 2'OH conformation to drive sugar repuckering, leading then to the formation of bioactive conformations. In summary, the 2'OH group seems to be a primary molecular switch contributing to specific protein-RNA recognition.

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Refinement of the AMBER Force Field for Nucleic Acids: Improving the Description of α/γ Conformers

Cited by 2,038 publications

References 62 publications

Spermine Condenses DNA, but Not RNA Duplexes

Spermine Condenses DNA, but Not RNA Duplexes

Mechanical Unfolding of the Beet Western Yellow Virus −1 Frameshift Signal

Small Details Matter: The 2′-Hydroxyl as a Conformational Switch in RNA

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