Conformational Preferences of DNA in Reduced Dielectric Environments

Abstract

The effect of reduced dielectric environments on the conformational sampling of DNA was examined through molecular dynamics simulations. Different dielectric environments were used to model one aspect of cellular environments. Implicit solvent based on the Generalized Born methodology was used to reflect different dielectric environments in the simulations. The simulation results show a tendency of DNA structures to favor noncanonical A-like conformations rather than canonical A- and B-forms as a result of the reduced dielectric environments. The results suggest that the reduced dielectric response in cellular environments may be sufficient to enhance the sampling of A-like DNA structures compared to dilute solvent conditions.

Microscopic picture of water-ethylene glycol interaction near a model DNA by computer simulation: Concentration dependence, structure, and localized thermodynamics

“…At first, we give some connection of the observations that came from the current work with the observations obtained in previous works. The effect of co-solute on the structural stability and dynamics of DNA was investigated in various previous works [ 27 , 79 – 84 ]. The major difference between those works and the current work is that in the present work both the local and global effects of crowding were investigated.…”

“…In one of the computational works, Yildirim et al . [ 27 ] used a reduced dielectric continuum medium to understand the conformational preference of DNA in the cellular-like environment and suggested that in the reduced dielectric medium, a canonical B form of DNA structure shifts towards non-canonical A form of the DNA structure.…”

Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen–purine linkage in the differential global genomic repair propensity

“…Although free energy methods that are theoretically more rigorous than end-point free energy methods such as the MM-PBSA method are available in the literature ( 61 , 62 ), a previous study has shown that DNA conformational free energy differences obtained using the MM-PBSA approach are in close agreement with the potentials of mean force determined using the more rigorous umbrella sampling approach ( 63 ). Although potential inaccuracies in free energy calculations may arise due to the theoretical simplicity of the MM-PBSA approach (e.g., implicit treatment of solvent), as well as limitations in our conformational sampling, the MM-PBSA free energies are expected to provide at least qualitative estimates of the energetic differences between possible conformations of damaged DNA ( 64 ). Furthermore, the choice of this method for the present application stems from our desire to compare the conformational preferences of ALII-N 2 -dG adducted DNA with those of ALII-N 6 -dA adducted DNA determined using the same protocol ( 46 ), as well as the successful applications of this method in previous studies of damaged DNA ( 50 , 65 – 67 ).…”

Identification of Key Interactions Between SARS-CoV-2 Main Protease and Inhibitor Drug Candidates

“…Molecular dynamics (MD) simulations, in which the dynamics of biopolymers in solution can be analyzed at the atomic level, is a typical SBDD method used to predict the interaction between proteins and inhibitors [23][24][25][26][27] . MD simulation is based on Newton's equation of motion and has been applied to biomolecules such as proteins, nucleic acids, and lipid membranes [28][29][30][31] . Recent studies have shown that MD simulations can be applied to clarify the binding mechanism between proteins and compounds at the molecular level, which is highly useful for rational drug design [23][24][25]32,33 .…”