Bello Martiniano, Fragoso-Vázquez M Jonathan, Correa Basurto José
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.
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.
Int J Biol Macromol. 2016 Nov;92:625-636. doi: 10.1016/j.ijbiomac.2016.07.071. Epub 2016 Jul 22.
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.
牛β-乳球蛋白（BLG）属于脂质运载蛋白家族。这是一组参与疏水分子结合与运输的蛋白质。实验和理论报告表明其在溶液中具有复杂的结构行为，在同二聚化和配体识别之间存在耦合效应。然而，迄今为止尚未有关于这种耦合效应成因的原子水平结构证据报道。为解决这一问题，将微秒级分子动力学（MD）模拟与分子力学广义玻恩表面积（MM/GBSA）方法、聚类分析和主成分分析（PCA）相结合，以探究BLG蛋白-蛋白自缔合以及单体和二聚体状态下棕榈酸（PLM）或十二烷基硫酸钠（SDS）配体识别的构象复杂性。与MM/GBSA方法相结合的MD模拟表明，二聚化对BLG的配体结合能力产生相反的影响。蛋白质二聚化降低了PLM亲和力，促进二聚体缔合。对于SDS，二聚体状态增加了亲和力，增强了二聚体解离。基于PCA的MD模拟表明，虽然对于PLM，游离单体和结合单体以及二聚体耦合之间在构象子空间中观察到的差异很小，但对于SDS，游离单体和结合单体以及二聚体耦合之间观察到了实质性变化。
