A molecular level picture of the stabilization of A-DNA in mixed ethanol–water solutions

Abstract

Advances in computer power, methodology, and empirical force fields now allow routine ''stable'' nanosecond-length molecular dynamics simulations of DNA in water. The accurate representation of environmental inf luences on structure remains a major, unresolved issue. In contrast to simulations of A-DNA in water (where an A-DNA to B-DNA transition is observed) and in pure ethanol (where disruption of the structure is observed), A-DNA in Ϸ85% ethanol solution remains in a canonical A-DNA geometry as expected. The stabilization of A-DNA by ethanol is likely due to disruption of the spine of hydration in the minor groove and the presence of ion-mediated interhelical bonds and extensive hydration across the major groove.

Energetics of Base Pairs in B-DNA in Solution: An Appraisal of Potential Functions and Dielectric Treatments

“…The results provided here, particularly the striking influence of sugar atoms on the base pair energies (as seen in Tables 1 and 2 with D(r) ) 1), do point to some scope for further finetuning of the partial atomic charges for an accurate modeling of DNA in solution. Molecular dynamics simulations on B-DNA and on A to B-DNA transitions [11][12][13][14][65][66][67][68] with explicit solvent, are better equipped to bring these issues to a sharper focus. In studies involving an implicit/continuum representation of the solvent, it is hoped that the results presented here would help in making a judicious choice of the dielectric function.…”

Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models

“…As noted, molecular dynamics simulations of d(CCAACGTTGG) 2 transition to B-DNA if started in the A form within ∼500 ps and stay in the B form if started there. On the other hand, the structure remains A if simulated in 85% ethanol, 14 so one has a stable A-DNA trajectory under such conditions. One can then calculate G h (B-DNA) and G h (A-DNA) in continuum water using eq 1 using "snapshots" from the trajectories in water and in 85% ethanol.…”

Solvation pressure in ethanol by molecular dynamics simulations

“…and Coulombic two-body terms, whose charges are given by the restrained electrostatic potential ͑RESP͒ model 18 as provided by Cheatham et al 19 All parameters are presented in Tables I-V.…”