Exploring DNA dynamics within oligonucleosomes with coarse-grained simulations: SIRAH force field extension for protein-DNA complexes

Brandner Giménez A, Schüller A, Melo F, Pantano SF (2018)

Publication Type: Journal article, Original article

Subtype: other

Publication year: 2018

Journal

Biochemical and Biophysical Research Communications Elsevier

Book Volume: 498

Pages Range: 319-326-326

Journal Issue: 2

DOI: 10.1016/j.bbrc.2017.09.086

Abstract

Describing the regulation of chromatin segments by protein recognition events constitute a major goal in biology and biotechnology. Despite astonishing experimental developments, achieving nearly atomistic spatial/temporal resolution on such macromolecular systems remains a big challenge owing to the intrinsic flexibility of large biological assemblies. Although computer simulations have become a reliable complement to experimental techniques, computational cost limits their routine applications to relatively small systems. However, the development of accurate and cost-effective coarse-grained (CG) models helps to bridge the gap between molecular dynamics simulations and biologically relevant scales. Performing an exhaustive search on a set of well-resolved crystallographic protein-DNA complexes, we introduced improvements on the CG SIRAH force field to describe protein-DNA interfaces. Modifications were validated against a set of non redundant structures and applied to the simulation of the longest DNA segment in complex with proteins that has been crystallized to date, i.e. a tetranucleosome. Multimicrosecond simulation of this small chromatin segment evidences a large mobility of the external DNA filaments, which is consistent with results from FRET experiments in solution. Moreover, we found that the sub-microsecond dynamics of DNA is strongly modulated by the quaternary structure, partially overcoming the intrinsic dynamics dictated by the primary structure.

Authors with CRIS profile

Astrid Brandner Giménez Professur für Computational Biology

Involved external institutions

Pontificia Universidad Católica de Chile CL Chile (CL) Institut Pasteur de Montevideo UY Uruguay (UY)

How to cite

APA:

Brandner Giménez, A., Schüller, A., Melo, F., & Pantano, S.F. (2018). Exploring DNA dynamics within oligonucleosomes with coarse-grained simulations: SIRAH force field extension for protein-DNA complexes. Biochemical and Biophysical Research Communications, 498(2), 319-326-326. https://dx.doi.org/10.1016/j.bbrc.2017.09.086

MLA:

Brandner Giménez, Astrid, et al. "Exploring DNA dynamics within oligonucleosomes with coarse-grained simulations: SIRAH force field extension for protein-DNA complexes." Biochemical and Biophysical Research Communications 498.2 (2018): 319-326-326.

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