Theoretical study of large conformational transitions in DNA: the B<–>A conformational change in water and ethanol/water.
|Theoretical study of large conformational transitions in DNA: the B<–>A conformational change in water and ethanol/water.
|Year of Publication
|Noy, Agnes, Pérez Alberto, Laughton Charles A., and Orozco Modesto
|Nucleic Acids Res
|A-Form, Computer Simulation, DNA, Ethanol, Models, Molecular, Nucleic Acid Conformation, Solvents, Water
We explore here the possibility of determining theoretically the free energy change associated with large conformational transitions in DNA, like the solvent-induced BA conformational change. We find that a combination of targeted molecular dynamics (tMD) and the weighted histogram analysis method (WHAM) can be used to trace this transition in both water and ethanol/water mixture. The pathway of the transition in the A–>B direction mirrors the B–>A pathway, and is dominated by two processes that occur somewhat independently: local changes in sugar puckering and global rearrangements (particularly twist and roll) in the structure. The B–>A transition is found to be a quasi-harmonic process, which follows closely the first spontaneous deformation mode of B-DNA, showing that a physiologically-relevant deformation is in coded in the flexibility pattern of DNA.