Ab initio determination of the flexibility of 2'-aminoribonucleosides and 2'-aminoarabinonucleosides inserted in duplexes

• Published in: Journal of computational chemistry Vol. 29; no. 9; pp. 1353 - 1363
• Main Authors: Barbe, Sophie, Le Bret, Marc
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.07.2008; Wiley Subscription Services, Inc; Wiley
• Subjects: Adenosine; Amino acids; Arabinonucleosides; Arabinonucleosides - chemistry; Biochemistry; Biological Physics; Cellular Biology; Computer Simulation; DNA; DNA - chemistry; hydration; Hydrogen Bonding; Life Sciences; Models, Chemical; modified nucleosides; Nucleic Acid Conformation; nucleic acid stability; Physics; quantum mechanics; Quantum Theory; Ribonucleosides; Ribonucleosides - chemistry; RNA; RNA - chemistry; solvation; Sugar; sugar puckering; Water; Water - chemistry; modified nucleoside; nucleic acid stability; solvation; quantum mechanic; hydration; sugar puckering
• ISSN: 0192-8651; 1096-987X
• DOI: 10.1002/jcc.20890

The sugar puckering of adenosine and uridine nucleosides with an amino group at 2' in the ribo or arabino orientations are determined using high-level quantum mechanical calculations Only the conformations that have dihedrals compatible with their insertion into a duplex are retained. The amino group has always been found to be pyramidal and its orientation governs the conformation of the sugar. The energetically most favorable conformation of the 2'-aminoribonucleosides has the south puckering but must be discarded. For another orientation of the 2'-amino group, the conformation is energetically less favorable but has the north puckering. Calculations performed in the presence of a water molecule give similar results but with a smaller energy gap. The model then explains why the insertion of a 2'-aminoribonucleotide destabilizes double-stranded RNAs and also double-stranded DNAs. In the arabino orientation, an NH₂ substituent at 2' favors north puckering. In contrast to 2'-aminoribonucleosides, deoxynucleosides inserted into a duplex remain in the most energetically favorable conformation compatible with the canonical values of the torsion angles. The whole relaxed potential map, in the amplitude/pseudorotation space, shows that for natural deoxyadenosine there is only one valley in the east running from south to north puckering.