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David E Draper

Publications and source records attributed to David E Draper.

6 recordsLinked to original sources
PubMed2004

A guide to ions and RNA structure.

RNA folding into stable tertiary structures is remarkably sensitive to the concentrations and types of cations present; an understanding of the physical basis of ion-RNA interactions is therefore a prerequisite for a quantitative accounting of RNA stability. This article summarizes the energetic factors that must be considered when ions interact with two different RNA environments. "Diffuse ions" accumulate near the RNA because of the RNA electrostatic field and remain largely hydrated. A "chelated" ion directly contacts a specific location on the RNA surface and is held in place by electrostatic forces. Energetic costs of ion chelation include displacement of some of the waters of hydration by the RNA surface and repulsion of diffuse ions. Methods are discussed for computing both the free energy of the set of diffuse ions associated with an RNA and the binding free energies of individual chelated ions. Such calculations quantitatively account for the effects of Mg(2+) on RNA stability where experimental data are available. An important conclusion is that diffuse ions are a major factor in the stabilization of RNA tertiary structures.

Animals↗
PubMed2003

Electrostatic interactions in a peptide--RNA complex.

Parallel experimental measurements and theoretical calculations have been used to investigate the energetics of electrostatic interactions in the complex formed between a 22 residue, alpha-helical peptide from the N protein of phage lambda and its cognate 19 nucleotide box B RNA hairpin. Salt-dependent free energies were measured for both peptide folding from coil to helix and peptide binding to RNA, and from these the salt-dependence of binding pre-folded, helical peptide to RNA was determined ( partial differential (DeltaG degrees (dock))/ partial differential log[KCl]=5.98(+/-0.21)kcal/mol). (A folding transition taking place in the RNA hairpin loop was shown to have a negligible dependence on salt concentration.) The non-linear Poisson-Boltzmann equation was used to calculate the same salt dependence of the binding free energy as 5.87(+/-0.22)kcal/mol, in excellent agreement with the measured value. Close agreement between experimental measurements and calculations was also obtained for two variant peptides in which either a basic or acidic residue was replaced with an uncharged residue, and for an RNA variant with a deletion of a single loop nucleotide. The calculations suggest that the strength of electrostatic interactions between a peptide residue and RNA varies considerably with environment, but that all 12 positive and negative N peptide charges contribute significantly to the electrostatic free energy of RNA binding, even at distances up to 11A from backbone phosphate groups. Calculations also show that the net release of ions that accompanies complex formation originates from rearrangements of both peptide and RNA ion atmospheres, and includes accumulation of ions in some regions of the complex as well as displacement of cations and anions from the ion atmospheres of the RNA and peptide, respectively.

Amino Acid Sequence↗
PubMed2003

A thermodynamic framework for the magnesium-dependent folding of RNA.

The goal of this review is to present a unified picture of the relationship between ion binding and RNA folding based on recent theoretical and computational advances. In particular, we present a model describing how the association of magnesium ions is coupled to the tertiary structure folding of several well-characterized RNA molecules. This model is developed in terms of the nonlinear Poisson-Boltzmann (NLPB) equation, which provides a rigorous electrostatic description of the interaction between Mg(2+) and specific RNA structures. In our description, most of the ions surrounding an RNA behave as a thermally fluctuating ensemble distributed according to a Boltzmann weighted average of the mean electrostatic potential around the RNA. In some cases, however, individual ions near the RNA may shed some of their surrounding waters to optimize their Coulombic interactions with the negatively charged ligands on the RNA. These chelated ions are energetically distinct from the surrounding ensemble and must be treated explicitly. This model is used to explore several different RNA systems that interact differently with Mg(2+). In each case, the NLPB equation accurately describes the stoichiometric and energetic linkage between Mg(2+) binding and RNA folding without requiring any fitted parameters in the calculation. Based on this model, we present a physical description of how Mg(2+) binds and stabilizes specific RNA structures to promote the folding reaction.

Binding Sites↗
PubMed2002

A compact RNA tertiary structure contains a buried backbone-K+ complex.

The structure of a 58 nucleotide ribosomal RNA fragment buries several phosphate groups of a hairpin loop within a large tertiary core. During refinement of an X-ray crystal structure containing this RNA, a potassium ion was found to be contacted by six oxygen atoms from the buried phosphate groups; the ion is contained completely within the solvent-accessible surface of the RNA. The electrostatic potential at the ion chelation site is unusually large, and more than compensates for the substantial energetic penalties associated with partial dehydration of the ion and displacement of delocalized ions. The very large predicted binding free energy, approximately -30 kcal/mol, implies that the site must be occupied for the RNA to fold. These findings agree with previous studies of the ion-dependent folding of tertiary structure in this RNA, which concluded that a monovalent ion was bound in a partially dehydrated environment where Mg2+ could not easily compete for binding. By compensating the unfavorable free energy of buried phosphate groups with a chelated ion, the RNA is able to create a larger and more complex tertiary fold than would be possible otherwise.

Base Sequence↗
PubMed2002

The linkage between magnesium binding and RNA folding.

Understanding the linkage between Mg(2+) binding and RNA folding requires a proper theoretical model describing the energetics of Mg(2+) binding to the folded and unfolded states of RNA. Our current understanding of Mg(2+) binding to these different RNA states derives from empirical thermodynamic models that depend on a number of unjustified assumptions. We present a rigorous theoretical model describing the linkage between RNA folding and magnesium ion binding. In this model, based on the non-linear Poisson-Boltzmann (NLPB) equation, the stabilization of RNA by Mg(2+) arises from two distinct binding modes, diffuse binding and site binding. Diffusely bound Mg(2+) are described as an ensemble of hydrated ions that are attracted to the negative charge of the RNA. Site-bound Mg(2+) are partially desolvated ions that are attracted to electronegative pockets on the RNA surface. We explore two systems, yeast tRNA(Phe) and a 58-nucleotide rRNA fragment, with different Mg(2+) binding properties. The NLPB equation accurately describes both the stoichiometric and energetic linkage between Mg(2+) binding and RNA folding for both of these systems without requiring any fitted parameters in the calculation. Moreover, the NLPB model presents a well-defined physical description of how Mg(2+) binding helps fold an RNA. For both of the molecules studied here, the relevant unfolded state is a disordered intermediate state (I) that contains stable helical secondary structure without any tertiary contacts. Diffusely bound Mg(2+) interact with these secondary structure elements to stabilize the I state. The secondary structural elements of the I state fold into a compact, native tertiary structure (the N state). Diffuse binding plays a dominant role in stabilizing the N state for both RNAs studied. However, for the rRNA fragment, site-binding to a location with extraordinarily high electrostatic potential is also coupled to folding. Our results suggest that much experimental data measuring the linkage between Mg(2+) binding and RNA folding must be reinterpreted.

Escherichia coli↗