Effect of arsenate substitution on phosphate repository of cell: a computational study

• Main Authors: Amit Singh, Kousik Giri
• Format: Article
• Language: English
• Published: The Royal Society 2018-01-01
• Series: Royal Society Open Science
• Subjects: quantum mechanics/molecular mechanics; dna modelling; arsenate hydrolysis; phosphate hydrolysis; quantum calculations
• Online Access: https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.181565

The structural analogy with phosphate derives arsenate into various metabolic processes associated with phosphate inside the organisms. But it is difficult to evaluate the effect of arsenate substitution on the stability of individual biological phosphate species, which span from a simpler monoester form like pyrophosphate to a more complex phosphodiester variant like DNA. In this study, we have classified the physiological phosphate esters into three different classes on the basis of their structural differences. This classification has helped us to present a concise theoretical study on the kinetic stability of phosphate analogue species of arsenate against hydrolysis. All the calculations have been carried out using QM/MM methods of our Own N-layer Integrated molecular Orbital molecular Mechanics (ONIOM). For quantum mechanical region, we have used M06-2X density functional with 6-31+G(2d,2p) basis set and for molecular mechanics we have used the AMBER force field. The calculated rate constants for hydrolysis show that none of the phosphate analogue species of arsenate has a reasonable stability against hydrolysis.