Glycine-Proline driven flexibility and interface-dependent conservation of six-residue {Omega}-loops in protein complexes

Interface-dependent conservation of six-residue {Omega}-loops is linked to constrained sequence space, with proline enriched at position four and glycine distributed across positions.

• Why it matters: {Omega}-loops sit on protein surfaces and participate in recognition and allosteric communication, but how their flexibility relates to evolutionary constraint across complex interfaces remains unclear.
• What they did: The authors curated six-residue {Omega}-loops from diverse protein-protein complexes, identifying 1205 hydrogen-bonded and 6518 non-hydrogen-bonded loops, then applied ProteinMPNN-based sequence design and Rate4Site evolutionary-rate analysis.
• The result: Interface loops in obligate homodimers and heterodimers were more conserved than non-interface loops, while transient and crystal dimers showed the opposite trend, and mapped human mutations plus a TEM1 {beta}-lactamase case illustrated functional consequences.

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