Molecular dynamics simulation on the selective interaction between fatty acid binding proteins and oleate

Abstract

Fatty Acid Binding Protein(FABP) usually binds a single molecule of long chain fatty acid and plays an important role in the "active lipid metabolism" in heart, liver, intestine and adipose tissues. Although the family of FABP has the highly structural homology, the binding affinity and the specificity are different. In order to investigate the selective interacitons between various FABPs and oleate, we performed Molecular Dynamics simulations on the complexes of FABP and oleate. We found that the dissociation constant($K_d$) of FABP-oleate complex is strongly related with the electrosatic interaction energy. At low $K_d$ the carboxyl group of oleate and Arg$^{106}$, Tyr$^{128}$, Arg$^{126}$ residues in the interior of FABP bind strongly. At high $K_d$ value the carboxyl group of oleate has moved to the β-D, β-E sheet region and are hydrogen-bonded with Arg$^{56}$, Arg$^{70}$ more weakly than those of low $K_d$. Also we found that the free water around oleate can affect the binding mode. At this point we propose the solvent-based specific interaction energy (SBSIE:$E_{ο-ρ}$/$E_{ο-ρ,ω}$, o:oleate, p:protein, w:water) which gives the effect of hydrophobic interaction in binding, and investigate the relation between the SBSIE and $K_d$ that gives more correlation than the relation between $K_d$ and the Interaction energy alone.