title: Refinement of the Sugar-Phosphate Backbone Torsion Beta for AMBER Force Fields Improves the Description of Z- and B-DNA.
abstract: Z-DNA duplexes are a particularly complicated test case for current force fields. We performed a set of explicit solvent molecular dynamics (MD) simulations with various AMBER force field parametrizations including our recent refinements of the ε/ζ and glycosidic torsions. None of these force fields described the ZI/ZII and other backbone substates correctly, and all of them underpredicted the population of the important ZI substate. We show that this underprediction can be attributed to an inaccurate potential for the sugar-phosphate backbone torsion angle β. We suggest a refinement of this potential, β(OL1), which was derived using our recently introduced methodology that includes conformation-dependent solvation effects. The new potential significantly increases the stability of the dominant ZI backbone substate and improves the overall description of the Z-DNA backbone. It also has a positive (albeit small) impact on another important DNA form, the antiparallel guanine quadruplex (G-DNA), and improves the description of the canonical B-DNA backbone by increasing the population of BII backbone substates, providing a better agreement with experiment. We recommend using β(OL1) in combination with our previously introduced corrections, εζ(OL1) and χ(OL4), (the combination being named OL15) as a possible alternative to the current β torsion potential for more accurate modeling of nucleic acids.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 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, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.|Institute of Biophysics, Academy of Sciences of the Czech Republic , Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Šponer
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka
authors.affiliation: Department of Medicinal Chemistry, University of Utah , 30 South 2000 East, Skaggs 105, Salt Lake City, Utah 84112, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Cheatham
authors.affiliation: Department of Medicinal Chemistry, University of Utah , 30 South 2000 East, Skaggs 105, Salt Lake City, Utah 84112, United States.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Jurečka
mesh_terms: D059371:DNA, B-Form / Q000737:chemistry*; D043542:DNA, Z-Form / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D010710:Phosphates / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D011789:Quantum Theory; D014867:Water / Q000737:chemistry
chemical_list: D059371:DNA, B-Form; D043542:DNA, Z-Form; D010710:Phosphates; D011134:Polysaccharides; D014867:Water