Conformational analysis of three pyrophosphate model species: Diphosphate, methyl diphosphate, and triphosphate

Abstract

Whereas theoretical investigations of the energetic origin of hydrolyzing a pyrophosphate linkage abound, few studies have focused on the energetics of the rotation of this linkage. This less-studied property of the pyrophosphate linkage was investigated here by use of ab initio calculations to characterize the conformational space of three model species of pyrophosphate anions: diphosphate (P2O), methyl diphosphate (CH3P2O), and triphosphate (P3O). By carefully selecting conformationally distinct rotational isomers of the three model compounds, their potential surfaces were thoroughly explored. In addition to showing that a terminal phosphate group is indeed very flexible in accordance with the general perception of free rotation, a number of intriguing features of this linkage emerged from the ab initio calculations, which include an influential sp3-hybridized CHO intramolecular hydrogen bond in methyl diphosphate, and a highly restricted rotational space pertaining to the central pyrophosphate linkage of the triphosphate anion. These ab initio findings were then evaluated by, and proved insightful in, follow-up examinations of experimentally determined complex structures of proteins and their dinucleotide or adenine and guanine triphosphate ligands. © 1999 John Wiley & Sons, Inc. J Comput Chem 20: 1702–1715, 1999