Trends for isolated amino acids and dipeptides: Conformation, divalent ion binding, and remarkable similarity of binding to calcium and lead

TL;DR

This study analyzes the structural conformations and binding energies of amino acids and dipeptides with various divalent cations, revealing similarities between calcium and lead binding that have implications for toxicity and ion mimicry.

Contribution

The paper provides a comprehensive first-principles dataset of amino acid and dipeptide conformations and their binding energies with multiple divalent cations, highlighting the similarity between calcium and lead interactions.

Findings

Few distinct backbone conformers dominate in isolated amino acids and dipeptides.

Divalent cation binding reduces conformational diversity and disrupts hydrogen bonding.

Calcium and lead exhibit nearly identical binding energies across amino acids and dipeptides.

Abstract

We derive structural and binding energy trends for twenty amino acids, their dipeptides, and their interactions with the divalent cations Ca$^{2+}$, Ba$^{2+}$, Sr$^{2+}$, Cd$^{2+}$, Pb$^{2+}$, and Hg$^{2+}$. The underlying data set consists of 45,892 first-principles predicted conformers with relative energies up to about 4 eV (about 400kJ/mol). We show that only very few distinct backbone structures of isolated amino acids and their dipeptides emerge as lowest-energy conformers. The isolated amino acids predominantly adopt structures that involve an acidic proton shared between the carboxy and amino function. Dipeptides adopt one of two intramolecular-hydrogen bonded conformations C$_5$ or equatorial C$_7$. Upon complexation with a divalent cation, the accessible conformational space shrinks and intramolecular hydrogen bonding is prevented due to strong electrostatic interaction of backbone and side chain functional groups with cations. Clear correlations emerge from the binding energies of the six divalent ions with amino acids and dipeptides. Cd$^{2+}$ and Hg$^{2+}$ show the largest binding energies - a potential correlation with their known high acute toxicities. Ca$^{2+}$ and Pb$^{2+}$ reveal almost identical binding energies across the entire series of amino acids and dipeptides. This observation validates past indications that ion-mimicry of calcium and lead should play an important role in a toxicological context.