Counterion condensation and shape within Poisson-Boltzmann theory.

An analytical approximation to the nonlinear Poisson-Boltzmann (PB) equation is applied to charged macromolecules that possess one-dimensional symmetry and can be modeled by a plane, infinite cylinder, or sphere. A functional substitution allows the nonlinear PB equation subject to linear boundary conditions to be transformed into an approximate linear (Debye-Hückel-type) equation subject to nonlinear boundary conditions. A simple analytical result for the surface potential of such polyelectrolytes follows, leading to expressions for the amount of condensed (or renormalized) charge and the electrostatic Helmholtz energy for polyelectrolytes. Analytical high-charge/low-salt and low-charge/high-salt limits are shown to be similar to results obtained by others based on PB or counterion condensation theory. Several important general observations concerning polyelectrolytes treated within the context of PB theory can be made including: (1) all charged surfaces display some counterion condensation for finite electrolyte concentration, (2) the effect of surface geometry is described primarily by the sum of the Debye constant and the mean curvature of the surface, (3) two surfaces with the same surface charge density and mean curvature condense approximately identical fractions of counterions, (4) the amount of condensation is not determined by a predefined "condensation distance" although such a distance can be determined uniquely from it, and (5) substantial condensation occurs if the Debye constant of the electrolyte is much less than the mean curvature of a highly charged polyelectrolyte.

Necessity of aromatic carboxylate anions to be planar to induce growth of cationic micelles.

It is well-known that some aromatic anions have the ability to induce viscoelastic transformation in aqueous solutions of cationic surfactants even at added salt concentrations as low as 10-20 mM. This behavior is associated with the formation of an entangled network of elongated micelles. However, the effect of aromatic ring substituents on the anion's ability to promote rapid micelle growth is not well-understood. We have performed ab initio calculations of the carbonyl group rotation barriers in a series of substituted benzoate and naphthoate anions at the MP2/STO-3G level of theory. It was found that aromatic carboxylates, known to be particularly effective in causing sphere-rod transition in cationic micelles, preferably adopt conformations with the COO(-) group in the same plane as the ring(s). This structural preference can be attributed to either intramolecular hydrogen bonding (o-hydroxyl derivatives) or pi-conjugation effects (m- and p-halogenated derivatives). In the former case the barrier to rotation is 40-50 kcal/mol, whereas in the latter case the threshold value is around 3.0 kcal/mol. Propensity for the planar conformation correlates with a greater depth of counterion penetration into the micelle surface, as inferred from NMR experiments, compared to the anions with less hindered carbonyl rotation. This points to favorable hydrophobic interactions between the surfactant methylene groups and the aromatic ring(s) of the anion as a possible explanation for the rapid growth of cationic micelles observed upon addition of certain aromatic carboxylates.

Calculation of the binding free energy for magnesium-RNA interactions.

The nature of the interaction between nucleic acids and divalent ions in solution is complex. It includes long-range electrostatic and short-range nonelectrostatic forces. Water molecules can be in an inner coordination shell that intervenes between the ion and its binding site. This work describes a method for calculating the binding free energy and applies it to a specific Mg-RNA system in the presence of monovalent salt. The approach combines high-level ab initio theory with Poisson-Boltzmann calculations and provides an accurate description of all terms of the binding free energy for magnesium ions located at the RNA surface (including nonelectrostatic interactions). Some alternative macroscopic approaches are also discussed.

In vitro translation and computational analyses of human profilin multimers.

Profilin is an ubiquitous intracellular G-actin and PIP2-binding protein that is a pan-allergen. Functional native human profilin multimers have recently been described, implicating regulatory roles in cell morphology, signaling and allergies. Considering the potential importance of profilin self-association in nature, multimerization was examined using cDNAs to human profilin I (P1) and II (P2) by employing a plasmid (pCITE2a+) for in vitro transcription/radiolabeled translation. Autoradiography of affinity column purified 35S-met-P1 or -P2 revealed predominant -14.8, 30 and 58 kDa bands that corresponded to parallel immunoblots using rabbit anti-human profilin antibodies. Reducing agents had no significant effect on the ratios of cpm associated with gel slices corresponding to 14.8/30/58 kDa profilin bands. Computer-based molecular modeling was used to further analyze a hypothetical structure for profilin multimers resistant to reducing agents. The crystalline P1 structure was downloaded and analyzed for likely sulphydryl bonding via the three integral cysteines (C16, C70, C127). All possible combinations of SH-bonds were investigated. The energetically most favorable dimer involved C16 + C127. 3-Dimensional conformation also revealed a protective pocket around the S-S bonds. The data show that, similar to native human and plant profilins, P1 and P2 cDNAs encode proteins that form fastidious multimers. A structure is proposed with relatively protected disulfide bridges between individual profilin moieties consistent with existing biochemical data.

The triplex-hairpin transition in cytosine-rich DNA.

We present a theoretical study of the self-complementary single-stranded 30-mer d(TC*TTC*C*TTTTCCTTCTC*CCGAGAAGGTTTT) (PDB ID: 1b4y) that was designed to form an intramolecular triplex by folding back twice on itself. At neutral pH the molecule exists in a duplex hairpin conformation, whereas at acidic pH the cytosines labeled by an asterisk (*) are protonated, forming Hoogsteen hydrogen bonds with guanine of a GC Watson-Crick basepair to generate a triplex. As a first step in an investigation of the energetics of the triplex-hairpin transition, we applied the Bashford-Karplus multiple site model of protonation to calculate the titration curves for the two conformations. Based on these data, a two-state model is used to study the equilibrium properties of transition. Although this model properly describes the thermodynamics of the protonation-deprotonation steps that drive the folding-unfolding of the oligomer, it cannot provide insight into the time-dependent mechanism of the process. A series of molecular dynamics simulations using the ff94 force field of the AMBER 6.0 package was therefore run to explore the dynamics of the folding/unfolding pathway. The molecular dynamics method was combined with Poisson-Boltzmann calculations to determine when a change in protonation state was warranted during a trajectory. This revealed a sequence of elementary protonation steps during the folding/unfolding transition and suggests a strong coupling between ionization and folding in cytosine-rich triple-helical triplexes.

Induced coalescence of cations through low-temperature Poisson-Boltzmann calculations.

The computational determination of preferred binding regions of divalent counterions to nucleic acids is either inaccurate (standard Poisson-Boltzmann approaches) or extremely time-consuming (Monte Carlo or molecular dynamics simulations). A novel "selective low-temperature" Poisson-Boltzmann method is introduced that, although approximate in nature, qualitatively accounts for ion correlation and charge-transfer effects and allows for the rapid determination of such regions through an "induced coalescence" of divalent ions. The method is illustrated here for the binding of Mg(2+) to a double-helical sequence of B-form DNA (CGCGAATTCGCG) but the technique is readily applicable to locating divalent cations in other systems such as DNA-endonuclease complexes and ribozymes.