Target Specific Conformational Flexibility and Electrostatic Complementarity Modulate LTNF10 Peptide Binding to Phospholipase A2 Variants from Snake Venoms

Lys5 substitution in the ten-residue peptide LTNF10 increases binding affinity to Group I svPLA2 variants from Elapidae by enhancing conformational flexibility and favorable binding conformations.

• Why it matters: Snake venom svPLA2 toxins damage tissues, and peptide inhibitors like LTNF10 need target-specific binding across diverse svPLA2 variants with different active-site microenvironments.
• What they did: The study prioritized LTNF10 from a curated inhibitor list, then compared LTNF10 and a D-to-K charge-modulating mutant at position 5 using free-energy landscapes and svPLA2 binding-pocket volume analysis across Group I (Elapidae) and Group II (Viperidae) variants.
• The result: Lys5 increases flexibility of mutant LTNF10 and is linked to reduced electrostatic repulsions and enhanced electrostatic interactions in Group I svPLA2 from Elapidae, while Group II svPLA2 from Viperidae shows reduced affinity with decreased flexibility and less pocket-volume change.

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