title: Energetic and conformational features linked to the monomeric and dimeric states of bovine BLG.
abstract: Bovine β-lactoglobulin (BLG) belong to the lipocalin family. This is a group of proteins involved in the binding and transporting of hydrophobic molecules. Experimental and theoretical reports have stated its complex structural behavior in solution, with coupled effects between homodimerization and ligand recognition. Nonetheless, structural evidence at the atomic level about the cause of this coupled effect has not been reported to date. To address this issue microsecond molecular dynamics (MD) simulations were combined with the molecular mechanics generalized Born surface area (MM/GBSA) approach, clustering analysis and principal component analysis (PCA), to explore the conformational complexity of BLG protein-protein self-association and palmitic acid (PLM) or dodecyl sulfate (SDS) ligand recognition in the monomeric and dimeric state. MD simulations, coupled to the MM/GBSA method, revealed that dimerization exerts contrasting effects on the ligand-binding capacity of BLG. Protein dimerization decreases PLM affinity, promoting dimer association. For SDS the dimeric state increases affinity, enhancing dimer dissociation. MD simulations based on PCA revealed that while few differences in the conformational subspace are observed between the free and bound monomer and dimer coupling for PLM, substantial changes are observed between the free and bound monomer and dimer coupling for SDS.
authors.affiliation: Laboratorio de Modelado Molecular, Bioinformática y Diseño de Fármacos de la Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col. Casco de Santo Tomas, Mexico City CP: 11340, Mexico. Electronic address: bellomartini@gmail.com.
authors.forename: Martiniano
authors.initials: M
authors.lastname: Bello
authors.affiliation: Laboratorio de Modelado Molecular, Bioinformática y Diseño de Fármacos de la Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col. Casco de Santo Tomas, Mexico City CP: 11340, Mexico.
authors.forename: M Jonathan
authors.initials: MJ
authors.lastname: Fragoso-Vázquez
authors.affiliation: Laboratorio de Modelado Molecular, Bioinformática y Diseño de Fármacos de la Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis Y Diaz Mirón S/N, Col. Casco de Santo Tomas, Mexico City CP: 11340, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Correa Basurto
mesh_terms: D000818:Animals; D002417:Cattle; D006860:Hydrogen Bonding; D007782:Lactoglobulins / Q000737:chemistry*; D008024:Ligands; D056004:Molecular Dynamics Simulation; D019308:Palmitic Acid / Q000378:metabolism; D025341:Principal Component Analysis; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D007782:Lactoglobulins; D008024:Ligands; D019308:Palmitic Acid; D012967:Sodium Dodecyl Sulfate; C028913:dodecyl sulfate
keywords: Binding free energy calculations; Dodecyl sulfate; Lactoglobulin; Molecular dynamics simulations; Palmitic acid