Conformational changes of surfactant protein B due to the alveolar air/liquid interface using molecular dynamics.

CONTEXT: Surfactant protein B (SP-B) is a critically important component of pulmonary surfactant (PS), responsible for much of the lipid restructuring activity necessary to maintain proper respiratory function. Despite its functional and biological importance, there is a significant lack of knowledge regarding the structural characteristics of SP-B, exacerbated by a lack of a complete, experimentally determined structure. Comparative modeling with homologous saposin-family proteins was used to generate predicted structures for SP-B in both an open (hydrophobic residues exposed) and closed (hydrophobic residues buried) conformation. These structures were then used for further study with molecular dynamics. Five replicate simulation systems were prepared for both conformations in different solvent conditions, including water and chloroform, a hydrophobic solvent. These simulations indicate the relative stability of the closed conformation protein in water, with the open conformation structure undergoing a large conformational change due to hydrophobic forces in water quantified by relevant intramolecular distances. Solvent distribution analysis elucidated the varying affinity of different regions of the protein to hydrophobic and hydrophilic environments, providing insight into the structural-functional characteristics of SP-B in the varied PS environment.

METHODS: For each system, a minimum of 900 ns production time per simulation was collected in 5 replicate simulations. Production time was measured after the system RMSD reached a steady state. All simulations used the FF19SB force field and OPC water model when applicable. Overall RMSD, per-residue RMSF, specific geometric parameters, and solvent distribution information were collected over the course of the simulations and analyzed.