B-DNA under stress: Over- and untwisting of DNA during molecular dynamics simulations

Srinivasaraghavan Kannan, Kai Kohlhoff, Martin Zacharias

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

The twist flexibility of DNA is central to its many biological functions. Explicit solvent molecular dynamics simulations in combination with an umbrella sampling restraining potential have been employed to study induced twist deformations in DNA. Simulations allowed us to extract free energy profiles for twist deformations and were performed on six DNA dodecamer duplexes to cover all 10 possible DNA basepair steps. The shape of the free energy curves was similar for all duplexes. The calculated twist deformability was in good agreement with experiment and showed only modest variation for the complete duplexes. However, the response of the various basepair steps on twist stress was highly nonuniform. In particular, pyrimidine/ purine steps were much more flexible than purine/purine steps followed by purine/pyrimidine steps. It was also possible to extract correlations of twist changes and other helical as well as global parameters of the DNA molecules. Twist deformations were found to significantly alter the local as well as global shape of the DNA modulating the accessibility for proteins and other ligands. Severe untwisting of DNA below an average of 25° per basepair step resulted in the onset of a global structural transition with a significantly smaller twist at one end of the DNA compared to the other.

Original languageEnglish
Pages (from-to)2956-2965
Number of pages10
JournalBiophysical Journal
Volume91
Issue number8
DOIs
StatePublished - Oct 2006
Externally publishedYes

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