PRELIMINARY COMPUTATIONAL STUDY OF THE PULMONARY SURFACTANT: A MOLECULAR DYNAMICS SIMULATION OF THE MINI-B PEPTIDE AND A DPPC MONOLAYERS

Pulmonary surfactant is a lipid–protein complex that reduces alveolar surface tension to near-zero values at end-expiration. Its most abundant phospholipid is DPPC, yet the hydrophobic protein SP-B is functionally indispensable and its congenital absence is lethal. No experimental structure of the mature 79-residue protein exists: every published simulation of "full-length SP-B" in fact simulates a homology model built on the saposin fold. This project avoids that uncertainty by starting from Mini-B, a 34-residue construct that preserves the N- and C-terminal amphipathic helices and their disulfide connectivity, and for which an NMR structure is available.  DPPC monolayers will be built at the air/water interface in the standard slab geometry: two opposing monolayers flanking a water layer, with the gas phase represented as a vacuum region along the box normal containing N2 molecules at 273 K. Systems are assembled in CHARMM-GUI and described by the CHARMM36m (protein) and CHARMM36 (lipid) force fields with TIP3 water. All simulations are run in GROMACS: an NVT stage equilibrates the bilayer precursor, after which the monolayer slab is generated and propagated in NPT at 273 K. The study is deliberately restricted to a quasi-equilibrium regime. Instead of a continuous compression, seven steps will be taken into account with fixed areas (45–90 Ų, finer between 55 and 65 Ų) are sampled independently. Each state is a well-defined NVT ensemble, so the surface tension obtained in GROMACS from the pressure tensor is a genuine ensemble average with statistical uncertainty from block averaging and independent replicas. Surface pressure is referenced to the surface tension of pure water computed with the same model and cutoffs. The isotherm is reconstructed point by point, and the compressibility modulus K_A = −A(∂π/∂A) is estimated. Finally this work will characterize at molecular level the behaviour of the  Pulmonary surfactant in presence of SP-B.