Theoretical study of large conformational transitions in DNA: the B<-->A conformational change in water and ethanol/water.
We explore here the possibility of determining theoretically the free energy change associated with large conformational transitions in DNA, like the solvent-induced B<-->A 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.
Noy
Agnes
A
Molecular Modeling and Bioinformatics Unit, Institut de Recerca Biomèdica & Instituto Nacional de Bioinformática, Parc Científic de Barcelona, Josep Samitier 1-5, Barcelona 08028, Spain.
Pérez
Alberto
A
Laughton
Charles A
CA
Orozco
Modesto
M
D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D044704:DNA, A-Form / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D044704:DNA, A-Form; D012997:Solvents; D014867:Water; D000431:Ethanol; D004247:DNA