Structure and dynamics of β-lactoglobulin in complex with dodecyl sulfate and laurate: A molecular dynamics study

Bovine beta-lactoglobulin (beta lg) is able to recognize a wide variety of hydrophobic ligands. Although binding promiscuity is characteristic of highly hydrophobic interactions, the structural plasticity of the beta lg binding cavity entrance seems to be crucial for the interaction with polar moieties, of different ligands. On the other hand, thermodynamic studies have shown that beta lg can associate to cognate ligands with distinctly different binding energetics, as in the case of the closely related molecules lauric acid (LA) and dodecyl sulfate (DS). In the recognition of LA, beta lg shows a classical hydrophobic signature (entropically driven), whereas the interaction of beta lg with DS exhibits a nonclassical hydrophobic signature (enthalpically driven). To gain insights into these opposed binding behaviors, MD simulations were carried out on beta lg in apo-form and bound to DS or LA. Overall, the results suggested that the distinct energetic signatures of these ligands come from distinct optimizations of both hydrophilic and hydrophobic contacts with the protein. (c) 2012 Elsevier B.V. All rights reserved.