Heteronuclear and homonuclear direct (D) and indirect (J) spin-spin interactions are important sources of structural information about nucleic acids (NAs). The Hamiltonians for the D and J interactions have the same functional form; thus, the experimentally measured apparent spin-spin coupling constant corresponds to a sum of J and D. In biomolecular NMR studies, it is commonly presumed that the dipolar contributions to Js are effectively canceled due to random molecular tumbling. However, in strong magnetic fields, such as those employed for NMR analysis, the tumbling of NA fragments is anisotropic because the inherent magnetic susceptibility of NAs causes an interaction with the external magnetic field. This motional anisotropy is responsible for non-zero D contributions to Js. Here, we calculated the field-induced D contributions to 33 structurally relevant scalar coupling constants as a function of magnetic field strength, temperature and NA fragment size. We identified two classes of Js, namely (1)JCH and (3)JHH couplings, whose quantitative interpretation is notably biased by NA motional anisotropy. For these couplings, the magnetic field-induced dipolar contributions were found to exceed the typical experimental error in J-coupling determinations by a factor of two or more and to produce considerable over- or under-estimations of the J coupling-related torsion angles, especially at magnetic field strengths >12 T and for NA fragments longer than 12 bp. We show that if the non-zero D contributions to J are not properly accounted for, they might cause structural artifacts/bias in NA studies that use solution NMR spectroscopy.

• Klíčová slova
• Dipolar coupling, Karplus equation, Magnetic susceptibility, Nucleic acid, Scalar coupling, Self-alignment,
• MeSH
• kvantová teorie MeSH
• magnetické pole * MeSH
• nukleární magnetická rezonance biomolekulární metody   MeSH
• nukleové kyseliny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nukleové kyseliny MeSH

We describe a novel, fundamental property of nucleobase structure, namely, pyramidilization at the N1/9 sites of purine and pyrimidine bases. Through a combined analyses of ultra-high-resolution X-ray structures of both oligonucleotides extracted from the Nucleic Acid Database and isolated nucleotides and nucleosides from the Cambridge Structural Database, together with a series of quantum chemical calculations, molecular dynamics (MD) simulations, and published solution nuclear magnetic resonance (NMR) data, we show that pyramidilization at the glycosidic nitrogen is an intrinsic property. This property is common to isolated nucleosides and nucleotides as well as oligonucleotides-it is also common to both RNA and DNA. Our analysis suggests that pyramidilization at N1/9 sites depends in a systematic way on the local structure of the nucleoside. Of note, the pyramidilization undergoes stereo-inversion upon reorientation of the glycosidic bond. The extent of the pyramidilization is further modulated by the conformation of the sugar ring. The observed pyramidilization is more pronounced for purine bases, while for pyrimidines it is negligible. We discuss how the assumption of nucleic acid base planarity can lead to systematic errors in determining the conformation of nucleotides from experimental data and from unconstrained MD simulations.

• MeSH
• deoxyadenosiny chemie   MeSH
• deoxycytidin chemie   MeSH
• dusík chemie   MeSH
• krystalografie rentgenová MeSH
• nukleární magnetická rezonance biomolekulární MeSH
• oligonukleotidy chemie   MeSH
• počítačová simulace MeSH
• purinové nukleosidy chemie   MeSH
• purinové nukleotidy chemie   MeSH
• puriny chemie   MeSH
• pyrimidinové nukleosidy chemie   MeSH
• pyrimidinové nukleotidy chemie   MeSH
• pyrimidiny chemie   MeSH
• sacharidy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2'-deoxyadenosine MeSH Prohlížeč
• deoxyadenosiny MeSH
• deoxycytidin MeSH
• dusík MeSH
• oligonukleotidy MeSH
• purinové nukleosidy MeSH
• purinové nukleotidy MeSH
• puriny MeSH
• pyrimidinové nukleosidy MeSH
• pyrimidinové nukleotidy MeSH
• pyrimidiny MeSH
• sacharidy MeSH