Molecular dynamic simulations reveal the structural determinants of Fatty Acid binding to oxy-myoglobin.
Authors: Chintapalli Sree V, Bhardwaj Gaurav, Patel Reema, Shah Natasha, Patterson Randen L, van Rossum Damian B, Anishkin Andriy, Adams Sean H
Journal: PloS one
Summary
# Editorial Summary Using computational modelling with equine myoglobin as their structural reference, researchers identified a specific fatty acid-binding pocket located in the hydrophobic cleft adjacent to the heme region, demonstrating that both saturated (palmitic) and unsaturated (oleic) fatty acids adopt characteristic U-shaped conformations stabilised by interactions with specific amino acid residues, particularly lysine residues 45 and 63. Molecular dynamic simulations revealed that the binding mechanism is oxygen-dependent: when myoglobin is oxygenated, it effectively sequesters fatty acids through coordinated interactions between the fatty acid carboxyl groups and lysine amino groups, whilst the alkyl tails nestle within a hydrophobic pocket formed by leucine, phenylalanine and valine residues. The saturated palmitic acid demonstrated greater conformational flexibility within the binding pocket, occasionally penetrating deeper into the cleft, whereas oleic acid's unsaturated structure allowed dual lysine coordination. These findings suggest myoglobin functions as an oxygen-regulated fatty acid transporter in muscle tissue—binding and sequestering fatty acids in the oxygenated state and releasing them as oxygen tension decreases—which has implications for understanding substrate availability during varying intensities of equine exercise and muscle metabolic efficiency. For equine professionals, this molecular understanding of myoglobin's role in fatty acid handling may inform future nutritional or conditioning strategies designed to optimise aerobic metabolism and sustained performance.
Read the full abstract on PubMed
Practical Takeaways
- •This computational research suggests myoglobin's oxygen-binding state directly regulates muscle fatty acid uptake and release, but clinical application to equine performance or conditioning requires experimental validation
- •Understanding fatty acid transport mechanisms at the molecular level may eventually inform nutrition and energy metabolism strategies for equine athletes, though practical implications are not yet established
- •The findings are primarily of academic/research interest; working equine professionals should await translational studies before applying these molecular insights to practice
Key Findings
- •Molecular dynamics simulations identified a fatty acid-binding site in myoglobin's hydrophobic cleft near the heme region using equine myoglobin as reference
- •Palmitic acid and oleic acid adopt U-shaped conformations with carboxyl groups coordinating to specific lysine residues (Lys45 for palmitic acid; Lys45 and Lys63 for oleic acid)
- •Oxygenated myoglobin binds fatty acids stably while deoxygenated myoglobin releases them, suggesting myoglobin functions as an oxygen-dependent fatty acid transporter in muscle