Computational Study of Pulmonary Surfactant Protein B Using Molecular Dynamics Simulations
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Pulmonary surfactant is a surface active lipid-protein complex covering the air-liquid interface at the surface of the alveoli in the lungs. Its main function is to reduce the surface tension at the interface, and thus to minimize the work of breathing and prevent the alveoli from collapsing at the end of the breathing cycle. Pulmonary surfactant protein B (SP-B) is an essential protein, necessary for the formation and maintaining of the film at the interface. Despite its importance, there has been no structural model for SP-B, or information about its molecular mechanism of function. In this thesis, we study the specific lipid interactions and membrane binding conformations of our new refined model for the SP-B hexamer of dimers. We use molecular dynamics simulations with the coarse-grained MARTINI force field for spontaneous lipid self-assembly and monolayer studies with SP-B. We concentrate on specific protein-lipid interactions, lateral lipid reorganization, and perturbations caused by SP-B in membranes. The results show specific lipid interaction sites in the structure of SP-B. We found that the protein causes lateral reorganization of lipids in monolayers and shows specificity towards phosphatidylglycerol and cholesterol. We further found that SP-B as a hexamer of dimers has specific membrane binding residues that orient the protein parallel to the surface of the membrane. SP-B causes lipid protrusions in monolayers and membranes. These results imply a molecular mechanism for lipid transfer through a SP-B oligomer ring in the surfactant.