The static and dynamic structural heterogeneities of B-DNA: extending Calladine-Dickerson rules
| Autor: | John H. Maddocks, Richard Lavery, Pablo D. Dans, Jürgen Walther, Modesto Orozco, Marco Pasi, Genís Bayarri, Alessandro S. Patelli, Alexandra Balaceanu, D. Petkevičiūtė |
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| Přispěvatelé: | Oxford University Press |
| Rok vydání: | 2019 |
| Předmět: |
base-pair
Base pair force-field Molecular Dynamics Simulation Biology 01 natural sciences Force field (chemistry) nmr Amino acid sequence 03 medical and health sciences Molecular dynamics Stochastic dynamics Seqüència d'aminoàcids 0103 physical sciences Genetics Statistical physics multimodality 030304 developmental biology Seqüència de nucleòtids 0303 health sciences Quantitative Biology::Biomolecules oligonucleotides Base Sequence 010304 chemical physics Anharmonicity Computational Biology unique tetranucleotide sequences DNA Complex network molecular dynamics microsecond molecular-dynamics nucleic-acids x-ray Harmonics conformations Harmonic model simulations DNA B-Form Nucleotide sequence |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Nucleic Acids Research |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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