Stacking Free Energy Profiles for All 16 Natural Ribodinucleoside Monophosphates in Aqueous Solution

Norberg, Jan; Nilsson, Lennart

doi:10.1021/ja00149a006

Cited by 110 publications

(121 citation statements)

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“…We report a free-energy difference of ∼14 kcal/mol between the closed and open conformations. The quantities are comparable if we account for the fact that the loss of the interactions involving residue A24 upon loop opening can be associated with 2-6 kcal/mol (for 1-4 kcal/mol for the loss of each stacked base [Norberg and Nilsson 1995] plus base solvation costs).…”

Section: Discussionmentioning

confidence: 99%

“…These interactions are always conserved when the ligand is present, and the loss of extra stacking interactions in the absence of the ligand can explain the difference of 10 kcal/mol between the energy profile in Figures 3 and 5. An early MD study reports 1-4 kcal/mol (depending on nucleotide type) for each stacked base that is lost (Norberg and Nilsson 1995). Moreover, the consequent solvation of the A73, U74, and U75 bases has to be counted in the energetic cost that the system has to pay.…”

Section: Add A-riboswitch Aptamer Bound To the Cognate Ligandmentioning

confidence: 99%

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Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study

Allnér

Nilsson

Villa

2013

RNA

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Riboswitches are mRNA-based molecules capable of controlling the expression of genes. They undergo conformational changes upon ligand binding, and as a result, they inhibit or promote the expression of the associated gene. The close connection between structural rearrangement and function makes a detailed knowledge of the molecular interactions an important step to understand the riboswitch mechanism and efficiency. We have performed all-atom molecular dynamics simulations of the adenine-sensing add A-riboswitch to study the breaking of the kissing loop, one key tertiary element in the aptamer structure. We investigated the aptamer domain of the add A-riboswitch in complex with its cognate ligand and in the absence of the ligand. The opening of the hairpins was simulated using umbrella sampling using the distance between two loops as the reaction coordinate. A two-step process was observed in all the simulated systems. First, a general loss of stacking and hydrogen bond interactions is seen. The last interactions that break are the two base pairs G37-C61 and G38-C60, but the break does not affect the energy profile, indicating their pivotal role in the tertiary structure formation but not in the structure stabilization. The junction area is partially organized before the kissing loop formation and residue A24 anchors together the loop helices. Moreover, when the distance between the loops is increased, one of the hairpins showed more flexibility by changing its orientation in the structure, while the other conserved its coaxial arrangement with the rest of the structure.

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Section: Discussionmentioning

confidence: 99%

Section: Add A-riboswitch Aptamer Bound To the Cognate Ligandmentioning

confidence: 99%

Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study

Allnér

Nilsson

Villa

2013

RNA

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“…A,G . C; Tables 2, 3) does not correspond to energetic values measured for base-stacking+ Turner and co-workers measured the free energy of base-stacking for 39-dangling ends and found that purines contributed 0+4-1+0 kcal/mol more than did pyrimidines (Freier et al+, 1986b)+ Calculations of base-stacking free energies for ribodinucleoside monophosphates also suggested a preference for the purine-purine interaction (Norberg & Nilsson, 1995)+ That these trends are not reflected in the data presented in this work suggests that the long-range displacements necessary for crosslinking of duplexes separated by a gap require overcoming an energetic barrier greater than the barrier to disrupt base-stacking+…”

Section: Comparison Of Data With Previous Studiesmentioning

confidence: 97%

A quantitative study of the flexibility contributed to RNA structures by nicks and single-stranded gaps

Cohen¹,

Cech²

1998

RNA

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Disulfide crosslinking via thiol-disulfide interchange was applied to quantitate the relative flexibility contributed by nicks and single-stranded gaps in an RNA structure. An RNA duplex comprised of three strands was constructed containing the disulfide crosslink precursors 1 and 2 at opposite ends of the duplex on opposite strands. The third strand was of varying length to yield a nick or single-stranded gaps of 1, 2, or 3 nt. Crosslinking rates indicated relative flexibilities of the resulting two-helix junctions. Crosslinking in the nicked duplex occurred two orders of magnitude slower than in a duplex containing a 3-nt gap. Rates of crosslinking in duplexes with 3-and 2-nt gaps showed only modest dependence on the gap sequence. Many natural RNAs, including ribozymes, contain two-helix junctions related to the model system described here. The data suggest that two-helix junctions containing a nick in one strand will retain substantial rigidity, whereas one or more single-stranded nucleotides at a two-helix junction allow significant flexibility.

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“…In ribodinucleoside monophosphates, the stacking preference follows the sequence purine-purine > purinepyrimidine pyrimidine-purine > pyrimidine-pyrimidine [124,125]. In particular, it was established that the stacked states have a 2-6 kcal mol lower free energy than the unstacked states for purine-purine dimers, while for pyrimidinepyrimidine dimers no appreciable barrier was obtained [124,126].…”

Section: The 3 5 Cgmp Polymerization Reactionmentioning

confidence: 99%

“…In particular, it was established that the stacked states have a 2-6 kcal mol lower free energy than the unstacked states for purine-purine dimers, while for pyrimidinepyrimidine dimers no appreciable barrier was obtained [124,126]. The most favorable stacking is found in A-A and G-G [120,122,123], determining their rapidly-obtained stacked state in the high dielectric aqueous solution [127].…”

Section: The 3 5 Cgmp Polymerization Reactionmentioning

confidence: 99%

Formamide and the origin of life

Saladino

Crestini

Pino

et al. 2012

Physics of Life Reviews

261

234

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The complexity of life boils down to the definition: "self-sustained chemical system capable of undergoing Darwinian evolution" (Joyce, 1994) [1]. The term "self-sustained" implies a set of chemical reactions capable of harnessing energy from the environment, using it to carry out programmed anabolic and catabolic functions. We briefly present our opinion on the general validity of this definition.Running anabolic and catabolic functions entails complex chemical information whose stability, reproducibility and evolution constitute the core of what is dubbed genetics.Life as-we-know-it is made of the intimate interaction of metabolism and genetics, both built around the chemistry of the most common elements of the Universe (hydrogen, oxygen, nitrogen, carbon). Other elements like phosphorus and sulphur play important but ancillary and potentially replaceable roles.The reproducible interaction of metabolic and genetic cycles results in the hypercycles of organization and de-organization of chemical information that we consider living entities. In order to approach the problem of the origin of life it is therefore reasonable to start from the assumption that both metabolism and genetics had a common origin, shared a common chemical frame, were embedded in physical-chemical conditions favourable for the onset of both.The most abundant three-atoms organic compound in interstellar environment is hydrogen cyanide HCN, the most abundant three-atoms inorganic compound is water H 2 O. The combination of the two results in the formation of formamide H 2 NCOH. We have explored the chemistry of formamide in conditions compatible with the synthesis and the stability of compounds of potential pre-genetic and pre-metabolic interest. We discuss evidence showing (i) that all the compounds necessary for the build-up of nucleic acids are easily obtained abiotically, (ii) that essentially all the steps leading to the spontaneous generation of RNA are abiotically possible, (iii) that the key compounds of extant metabolic cycles are obtained in the same chemical frame, often in the same test tube.How close are these observations to a plausible scenario for the origin of life?

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Stacking Free Energy Profiles for All 16 Natural Ribodinucleoside Monophosphates in Aqueous Solution

Cited by 110 publications

References 0 publications

Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study

Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study

A quantitative study of the flexibility contributed to RNA structures by nicks and single-stranded gaps

Formamide and the origin of life

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