Stacking geometry between two sheared Watson-Crick basepairs: Computational chemistry and bioinformatics based prediction.
BACKGROUND
Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The A:A w:wC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Its effect is pronounced when the A:A w:wC basepair stacks on Sheared wobble G:U W:WC basepairs.


METHODS
We employed molecular dynamics simulations of three possible double helices with GAG, UAG and GAU sequence motifs at their centers and quantum chemical calculation for non-canonical A:A w:wC basepair stacked on G:U W:WC basepair.


RESULTS
We noticed stable structures of GAG motif with specifically negative Shear of the A:A basepair but stabilities of the other motifs were not found with A:A w:wC basepairing. Hybrid DFT-D and MP2 stacking energy analyses on dinucleotide step sequences, A:A w:wC::G:U W:WC and A:A w:wC::U:G W:WC reveal that viable orientation of A:A::G:U prefers one of the H-bonding modes with negative Shear, supported by crystal structure database. The A:A::U:G dinucleotide, however, prefers structure with only positive Shear.


CONCLUSIONS
The quantum chemical calculations explain why MD simulations of GAG sequence motif only appear stable. In the cases of the GAU and UAG motifs "tug of war" situation between positive and negative Shears of A:A w:wC basepair induces conformational plasticity.


GENERAL SIGNIFICANCE
We have projected comprehensive reason behind the promiscuous nature of A:A w:wC basepair which brings occasional structural plasticity.
['Maiti|Satyabrata|S|', 'Mukherjee|Debasish|D|', 'Roy|Parthajit|P|', 'Chakrabarti|Jaydeb|J|', 'Bhattacharyya|Dhananjay|D|']
D000225:Adenine D020029:Base Pairing D019295:Computational Biology D000080486:Computational Chemistry D018360:Crystallography, X-Ray D015226:Dinucleoside Phosphates D006860:Hydrogen Bonding D056004:Molecular Dynamics Simulation D015394:Molecular Structure D009690:Nucleic Acid Conformation D012313:RNA
RNA double helices Basepair stacking Molecular dynamics simulation Conformational plasticity Density functional theory Flanking basepair effect