title: On the Use of Molecular Dynamics Simulations for Probing Allostery through DNA.
abstract: A recent study described an allosteric effect in which the binding of a protein to DNA is influenced by another protein bound nearby. The effect shows a periodicity of ∼10 basepairs and decays with increasing protein-protein distance. As a mechanistic explanation, the authors reported a similar periodic, decaying pattern of the correlation coefficient between major groove widths inferred from a shorter molecular dynamics simulation. Here we show that in a state-of-the-art, microsecond-long simulation of the same DNA sequence, the periodicity of the correlation coefficient is not observed. To study the problem further, we extend an earlier mechanical model of DNA allostery based on constrained minimization of effective quadratic deformation energy of the DNA. We demonstrate that, if the constraints mimicking the bound proteins are properly applied, the periodicity in the binding energy is indeed recovered.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Dršata
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Zgarbová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Jurečka
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic; Central European Institute of Technology, Campus Bohunice, Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Šponer
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Laboratory of Informatics and Chemistry, University of Chemistry and Technology Prague, Prague, Czech Republic. Electronic address: lankasf@vscht.cz.
authors.forename: Filip
authors.initials: F
authors.lastname: Lankaš
mesh_terms: D000494:Allosteric Regulation; D004247:DNA / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA
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