Premium
Calculations on the effect of methylation on the electrostatic stability of the B‐ and Z‐conformers of DNA
Author(s) -
Pack George R.,
Prasad C. V.,
Salafsky Joshua S.,
Wong Linda
Publication year - 1986
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360250912
Subject(s) - conformational isomerism , chemistry , ionic strength , counterion , ionic bonding , electrolyte , poisson–boltzmann equation , charge density , crystallography , ion , computational chemistry , thermodynamics , aqueous solution , molecule , organic chemistry , physics , electrode , quantum mechanics
Abstract The three‐dimensional Poisson–Boltzmann equation for the distribution of counterion charge density around double‐helical DNA has been solved for solutions of .01 M , .10 M , and .20 M monovalent salt. The polymers, poly[d(CpGp)] and poly[d(m 5 CpGp)], were studied in the B‐ and the Z‐conformations. The effect of methylation on the relative stabilities of these conformers in solutions of different ionic strengths is known to favor the Z‐form. Accumulation of charge density around the B‐ and the Z‐conformers is compared in detail. The relative electrostatic stabilities of the B‐ and Z‐conformers in .01 M , .10 M , and .20 M solutions are compared and discussed in terms of the ion–DNA interactions and the self‐energy of the structured ionic environment. The ion–DNA interaction energies, termed “phosphate screening,” monotonically decrease with ionic strength and are consistent with a B‐to‐Z conformation change induced in either polymer by increased electrolyte concentration. However, these calculated energies alone do not account for the fact that the ionic strength at the midpoint of the transition of the methylated polymer is substantially lower than that of its unmethylated analogues. The phosphate screening effect is counterbalanced by changes in the self‐energy required for the creation of the structured counterion environment. This self‐energy of the electrolyte environment monotonically increases with ionic strength. Methylation‐induced shifts in the overall conformational equilibria depend on the relative changes of these competing effects. Increasing salt concentration is calcualted to favor the Z‐conformer. The effect of methylation, lowering the ionic strength of the transition midpoint, is proposed to originate in minor structural changes in the Z‐form of the polymer, making the groove more accessible to counterions in the G(3′ – 5′)C region. This allows a redistribution of counterion density and a lowering of the self‐energy of the ionic environment, conferring added stability to the Z‐conformation, as indicated by calculations of relative entropies. The experimentally observed temperature dependence of the B‐to‐Z transition, however, cannot be explained without assuming the release of bound water. Maps of the calculated three‐dimensional structure at the counterion distribution near the surface of these molecules in both the B‐ and the Z‐forms are also presented.