Date Published: April 01, 2019
Publisher: International Union of Crystallography
Author(s): Miroslaw Gilski, Jianbo Zhao, Marcin Kowiel, Dariusz Brzezinski, Douglas H. Turner, Mariusz Jaskolski.
Revised geometrical parameters are proposed for the Watson–Crick pairs of nucleobases, for use as restraints in modeling and refinement of the structures of nucleic acids. Accurate values of these parameters were derived (and compared) from small-molecule Cambridge Structural Database structures, from super accurate ultrahigh-resolution nucleic acid structures in the Protein Data Bank, and from quantum mechanical calculations. The effect of base pairing on the molecular geometry of the nucleobases is also investigated.
In the following subsections, we present a number of comparisons of results obtained using the different sources of structural information (I, II, III) as outlined above. We end each of the comparisons with a succinct conclusion. Those partial conclusions are recapitulated in the Discussion, which provides a general summary.
Advanced QM calculations in Gaussian 09 are capable of producing quite good molecular geometry for nucleobases, and the results are consistent across different parametrizations, provided a sufficiently high level of theory is used, such as the aug-cc-pVTZ basis set used in this study. In particular, the QM models correctly distinguish between isolated and WC-paired bases. The best source of reference geometry for paired bases are ultrahigh-resolution nucleic acid structures in the PDB. However, the nucleobase geometry derived from small-molecule crystal structures (of usually unpaired but hydrogen-bonded bases) in the CSD is also a realistic representation of the geometry found in WC pairs of nucleic acids duplexes. Thus, CSD-based compilations, such as the standard Parkinson library, or its updated version presented in this work and available for practical applications via our RestraintLib web server, are a legitimate source of restraint targets for macromolecular refinement. Moreover, on scrupulous pairwise comparisons with the reference PDB structures, the CSD parameters are still superior to those derived by QM calculations. However, for non-canonical bases, such as iC and iG, for which no reliable experimental structural information is available, the QM geometry is currently the best source of stereochemical restraint targets.