[Mg spin determines adenosinetriphosphate energetics]

Area of Science:

• Computational Chemistry
• Biophysical Chemistry
• Quantum Chemistry

Context:

• Adenosinetriphosphate (ATP) hydrolysis is crucial for cellular energy.
• Magnesium ions (Mg2+) are essential cofactors in biological processes involving ATP.
• Understanding the molecular mechanisms of ATP interaction with Mg2+ is key to elucidating energy transduction.

Purpose:

• To investigate the interactions between ATP and a magnesium cofactor ([Mg(H2O)6]2+) in a water environment using molecular dynamics.
• To explore the potential energy surfaces (PESs) in singlet (S) and triplet (T) states.
• To elucidate the reaction pathways and intermediate states leading to ATP cleavage.

Summary:

• Molecular dynamics simulations using DFT:B3LYP identified distinct interaction pathways for the Mg cofactor with ATP in singlet and triplet states.
• Chelation of ATP's phosphate groups by Mg2+ leads to stable and metastable complexes, differing in hydration.
• An intersection of triplet PESs creates an unstable state, facilitating ATP cleavage via an ion-radical pathway, producing *AMP-.

Impact:

• Provides a detailed molecular-level understanding of ATP hydrolysis mechanisms.
• Explains the formation of reactive intermediates like *AMP-, previously observed in Chemically Induced Dynamic Nuclear Polarization (CIDNP) experiments.
• Offers insights into the role of magnesium in ATP energy release and potential biological consequences.