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 7−4), methyl diphosphate (CH3P2O 7−3), and triphosphate (P3O 10−5). 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

Development of polyphosphate parameters for use with the AMBER force field

“…Visualization of the normal modes of the minima of MDP and MTP (calculated with Gaussian 98), revealed a particularly soft normal mode (49.3 cm −1 and 85.6 cm −1 )13 for the P–OS–P angles in both polyphosphates. This has been noted previously by Hwang et al8 and in the parameterization of polyphosphates for the CHARMM force field 4. The estimated P–OS–P angle parameters in the AMBER force field appear to have been taken by analogy from the CT–OS–P angle; however, the normal modes that involve the CT–OS–P bend have much higher frequencies in these molecules (198.7 and 282.1 cm −1 in the frequency calculations using Gaussian 98) 13.…”

“…Our initial ab initio molecular orbital calculations were based on the conformations of MDP and MTP determined at the RHF/6‐31G* level by Hwang et al8 In the gas phase, the lowest energy conformations of MTP and MDP contain an intramolecular “hydrogen bond” interaction between a terminal anionic oxygen and a hydrogen of the methyl group. This interaction is unlikely in biological systems due to the presence of solvent molecules and counter ions.…”

Ab initio studies on the tri- and diphosphate fragments of adenosine triphosphate

“…Similar reasons can be given to explain the exothermicity of reactions R1, R2 and R5. Electrostatic repulsions clearly are responsible for this exothermicity, which has been pointed out by experiments and earlier calculations [8][9][10][11][12][13][14][15][16][17].…”

“…They have also predicted the aqueous phase hydration energy using several methods based on a dielectric continuum model of the aqueous solvent. Recently, the energetics of the rotation of the pyrophosphate linkage has also been investigated by the use of ab initio calculations by Hwang et al [17]. They have explored the potential energy surface of three pyrophosphate prototypes using HF/6-31G* basis set.…”

Conformational behavior of nucleotide-sugar in solution: Molecular dynamics and NMR study of solvated uridine diphosphate-glucose in the presence of monovalent cations

“…Since only one crystal structure, the sodium salt of uridinediphospho–glucose (UDP–Glc),12 has been solved until now, conformational study of the nucleotide–sugars was approached by computational chemistry methods. Model compounds such as dimethyl pyrophosphate13–15 or sugar–phosphate16–18 were first studied with the use of ab initio calculations. Energy parameters were then derived for the AMBER force field17 and added to Glycam‐93, the preexisting carbohydrate parameterization 19.…”