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Anion–π contacts are common in the PDB

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A PDB-wide search finds anion–π interactions in most protein structures, with Asp/Glu carboxylates packing on aromatics and frequent cation–π partners opposite.

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A thorough anion-π interaction study in biomolecules: on the importance of cooperativity effects

Lucas X, Bauzá A, Frontera A, et al. · Chemical science · 2016

doi.org/10.1039/c5sc01386kRead the full paper ↗140 citationscc by

What they did

Authors scanned the PDB for anion–π pairs among carboxylates, phosphates, and aromatic side chains/nucleobases, classified geometry, tested enrichment statistically, and looked for ternary anion–π–cation and anion–π–π contacts that could cooperate.

What they found

Thousands of anion–π contacts exist. 61.3% of 62 033 processed PDB structures contain them. Asp/Glu dominate with near-parallel carboxylates; His is the most common protein aromatic, but Tyr rises at interfaces. DNA vs RNA differ in Glu/Asp and base preferences. Opposite-face cation–π and stacking are common, implying cooperativity.

The limits

What it doesn't show

This is a structural census, not a measured binding free energy for a designed host; predicted cooperativity is inferred from geometry, not from a new titration series.

Key terms

Anion–π interaction
Contact between an anion (often carboxylate) and the face of an aromatic ring.
Cooperativity
A second interaction (cation–π or stacking) on the same ring that can strengthen a weak anion–π contact.
Cation–π
Attraction of a cation to an aromatic face, often opposite the anion here.
PDB census
Statistical search of deposited crystal/NMR structures for a contact type.
Close-to-parallel carboxylate
Preferred orientation of Asp/Glu relative to the aromatic plane.

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Fraction of processed PDB entries with anion–π contacts:

Common questions

How common are anion–π contacts in proteins?

In 61.3% of processed PDB structures.

Which anions dominate?

Asp and Glu carboxylates.

Which protein aromatic is most common?

His overall; Tyr at interfaces.

DNA vs RNA?

DNA shows no Glu/Asp selectivity; Glu is more present in RNA, with different base partners.

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