75616
Molecular Dynamics Simulations of Surfactant Protein B Peptides
Jennifer Lester
Mentor: Douglas Tobias
Normal human respiration depends on the presence of a surface active agent (surfactant) located in the alveolar airsacs of the lung. Functional components of pulmonary surfactant include phospholipids and specific proteins that decrease surface tension in the alveoli and substantially reduce the work involved in breathing. Pulmonary diseases associated with improper surfactant function include Neonatal Respiratory Distress Syndrome and Acute Respiratory Distress Syndrome. The design of effective therapies requires knowledge of the composition and interactions between each of the surfactant components. To analyze these interactions closely at the atomic level, molecular dynamics simulations were carried out on a model system containing a Palmitic Acid monolayer and the surfactant protein B (SP-B) peptide. The model system maintained its stability through electrostatic interactions between the charged residues of the peptide and the hydrophilic head groups of the lipid, and between the aromatic residues of the peptide and the hydrophobic tail region of the lipids. To determine the specific role of the charged residues, the four cationic residues were removed in a model mutant SP-B1-25, which was also simulated. Similarly, the aromatic residues of SP-B1-25 were removed in a separate model mutant and simulated. A third mutant, lacking all aromatic and other bulky neutral residues, was directly compared to the previously described mutant to determine specifically the role of aromatic groups. Lastly, a fourth mutant, lacking charged and aromatic residues, was simulated to determine the role of sequence specificity. Comparison of the mutants and the native revealed that the presence of the charged and aromatic residues affect the orientation and secondary structure of the peptide as well as the order of the lipids in the monolayer.