B-DNA Under Stress: Over and Un-Twisting of DNA during Molecular Dynamics Simulations
Srinivasaraghavan Kannan 1, Kai Kohlhoff 1 and Martin Zacharias 1*
1 International University Bremen
* To whom correspondence should be addressed. E-mail: m.zacharias{at}iu-bremen.de.
Submitted on April 13, 2006
Revised on June 1, 2006
Accepted on 23 June 2006
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Abstract |
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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 to extract free energy profiles for twist deformations and were performed on six DNA dodecamer duplexes to cover all 10 possible DNA base-pair 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 base pair steps on twist stress was highly non-uniform. 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 un-twisting of DNA below an average of 25° per base-pair 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.
Key Words:
DNA deformation, DNA recognition, DNA supercoiling, free energy simulation, nucleic acid flexibility, potential of mean force
