Arsenic-nucleotides interactions: an experimental and computational investigation

Area of Science:

• Environmental Chemistry
• Biochemistry
• Computational Chemistry

Background:

• Arsenic (As(iii)) is a known carcinogen, but its interactions with biological molecules remain unclear.
• The binding properties of As(iii) with common nucleotides like AMP, ADP, and ATP are largely unknown.

Purpose of the Study:

• To investigate the stability of complexes formed between arsenic and nucleotides (AMP, ADP, ATP).
• To elucidate the binding mechanisms and relative affinities of As(iii) for these nucleotides.

Main Methods:

• Potentiometric and calorimetric measurements to assess complex stability across different pH levels.
• Ab initio molecular dynamics (AIMD) and metadynamics (MetD) simulations to analyze binding interactions at the atomic level.

Main Results:

• A clear hierarchy of arsenic binding stability was observed: ATP > ADP > AMP.
• ATP demonstrated a greater number of effective binding sites for As(iii) compared to AMP.
• Free energy calculations quantitatively confirmed ATP's superior chelating effectiveness for arsenic.

Conclusions:

• Adenosine triphosphate (ATP) is a more effective chelating agent for arsenic (As(iii)) than ADP or AMP.
• The enhanced binding of As(iii) to ATP is attributed to its greater number of binding sites and favorable interaction energies, influencing arsenic's behavior in biological systems.