Bending of DNA by Asymmetric Charge Neutralization:  All-Atom Energy Simulations

Abstract

DNA dodecamers of the alternating d(CG).d(CG) sequence with six phosphate groups either charge-neutralized or substituted by neutral methylphosphonates across the major or minor groove have been subjected to energy minimization to determine the conformational effect of the asymmetric elimination of phosphate charge. We report bending angles, directions of bending, and detailed structural characteristics such as groove widths and local base-pair parameters. Our principal results are that charge neutralization on one face of the DNA induces significant bending toward the neutralized face, in agreement with theoretical predictions on a simplified model and experimental data on a similar base-pair sequence, and that the DNA conformation averaged over all stereospecific methylphosphonate substitutions is nearly the same as the conformation produced by charge neutralization of the phosphates. Individual isomers, however, cover a wide range of structures, with the magnitude and direction of overall bending sensitive to the precise stereochemical pattern of neutralization. Our simulation does not explicitly contain counterions, and the results therefore suggest that counterions can influence DNA structure by neutralizing the phosphate charge. These data provide new hints into the molecular mechanisms which underlie the deformations of DNA structure induced by the binding of positively charged proteins and other tightly associated cationic species.

The DNA Structure Responds Differently to Physiological Concentrations of K+ or Na+

“…Of course, the cations could also act on DNA structure and readout via a more conventional "electrostatic collapse" mechanism, where the DNA bends towards its side partially neutralized by the bound cations. 9,58,59 We note that, in general, such electrostatic collapse mechanism may well coexist with modulation of the BII populations, although deconvoluting the two contributions may prove impractical.…”

“…Electrophoretic phasing experiments showed that ammonium ions tethered to one face of double-helical DNA caused it to bend, 58 possibly mimicking the effect of a bound protein, but it is unclear how these results relate to the effect of free ions on noncomplexed DNA. Monitoring of base-pair opening in various NH 4 + and Na + buffers suggested that the type of counterion affected the DNA structure, via environment-dependent changes in the chemical shifts of adenine H2 atoms.…”

A walk though vertebrate and invertebrate protamines

“…Although whether these highly charged proteins bind to either the major or minor groove of DNA has long been debated [see Raukas and Mikelsaar (1999) for a recent review], the argument appears to be finally settled in favor of the major groove (Subirana 1991). The charge neutralization resulting from this interaction is responsible for the bending of DNA (Kosikov et al 2002) that ultimately results in the highly compact toroidal nucleoprotamine structures (Brewer et al 1999) observed in mammalian sperm (Ward and Coffey 1991;Balhorn et al 1999) or in the globular or lamellar structures observed in the sperm of other vertebrates (Gusse and Chevaillier 1978) and invertebrates (Suzuki and Wakabayashi 1988;Caceres et al 1999;Gimenez-Bonafe et al 2002). The occurrence of cysteine provides an efficient mechanism to form interchromatin fiber associations (see Balhorn et al 1992Balhorn et al , 1999Gimenez-Bonafe et al 2002).…”

Simple Model for Overcharging of a Sphere by a Wrapped Oppositely Charged Asymmetrically Neutralized Polyelectrolyte: Possible Effects of Helical Charge Distribution

“…(DNA helicity was however shown to be important in all-atom computer simulations of the bending of asymmetrically neutralized DNA. 23 )…”