The static and dynamic structural heterogeneities of B-DNA: extending Calladine-Dickerson rules.

Abstract:

:We present a multi-laboratory effort to describe the structural and dynamical properties of duplex B-DNA under physiological conditions. By processing a large amount of atomistic molecular dynamics simulations, we determine the sequence-dependent structural properties of DNA as expressed in the equilibrium distribution of its stochastic dynamics. Our analysis includes a study of first and second moments of the equilibrium distribution, which can be accurately captured by a harmonic model, but with nonlocal sequence-dependence. We characterize the sequence-dependent choreography of backbone and base movements modulating the non-Gaussian or anharmonic effects manifested in the higher moments of the dynamics of the duplex when sampling the equilibrium distribution. Contrary to prior assumptions, such anharmonic deformations are not rare in DNA and can play a significant role in determining DNA conformation within complexes. Polymorphisms in helical geometries are particularly prevalent for certain tetranucleotide sequence contexts and are always coupled to a complex network of coordinated changes in the backbone. The analysis of our simulations, which contain instances of all tetranucleotide sequences, allow us to extend Calladine-Dickerson rules used for decades to interpret the average geometry of DNA, leading to a set of rules with quantitative predictive power that encompass nonlocal sequence-dependence and anharmonic fluctuations.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Dans PD,Balaceanu A,Pasi M,Patelli AS,Petkevičiūtė D,Walther J,Hospital A,Bayarri G,Lavery R,Maddocks JH,Orozco M

doi

10.1093/nar/gkz905

subject

Has Abstract

pub_date

2019-12-02 00:00:00

pages

11090-11102

issue

21

eissn

0305-1048

issn

1362-4962

pii

5590661

journal_volume

47

pub_type

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