Fig 1.
A) Atomistic (left) and coarse-grained (right) model of surfactant protein C (SP-C). B) Chemical structure of lipids used to mimic the pulmonary surfactant membrane: DPPC, POPC, POPG, and cholesterol (CHOL). See the text for details.
Table 1.
Detailed composition of the systems studied in this work.
Fig 2.
The definition of ϕ1 and ϕ2 dihedral angles.
The centers of mass (COMs) of the upper (A/A’), middle (B/B’), and lower (C/C’) groups of residues were picked as the three points forming each dihedral, while the fourth point (C’/C) belonged to the other monomer. The upper points (A/A’) were defined as the COM of LEU31, LEU32, and MET33 in each SP-C monomer. The middle points (B/B’) were defined as COM of VAL17, VAL18, and VAL19. Finally, the lowest points (C/C’) were defined as COM of VAL8, ASN9, and LEU10.
Fig 3.
A) The SP-C dimerization free energy as a function of the minimum distance between any two beads belonging to SP-C monomers. Structures with dmin smaller or equal to 0.60 nm (depicted as black dashed line) are considered the bound dimers. We marked the untapped region of the free energy profile with a blue dashed line. B) The average minimum distance between N-termini (residues 8–10; green line), middles of helices (residues 17–19; orange line), and C-termini (residues 31–33; blue line) of SP-C monomers as a function of the COM-COM distance between SP-C monomers.
Fig 4.
Representative structures (centroids) of three distinctive topologies of the SP-C homodimer ordered by the increasing free energy values: (A) parallel dimer, (B) inverted V-shape dimer, and (C) V-shape dimer. The SP-C monomers involved in the formation of homodimers are colored differently (orange and lime) for clarity.
Fig 5.
The distributions of the minimum distances between N-termini (green line), middles of helices (orange line), and C-termini (blue line) of SP-C monomers in each dimer topology: A) parallel dimer, B) inverted V-shape dimer, and C) V-shape dimer.
Fig 6.
The distributions of the crossing angles (Ψ) between the helices forming the homodimer in each dimer topology: A) parallel dimer, B) inverted V-shape dimer, and C) V-shape dimer.
Fig 7.
Contact probability maps for each pair of residues in the SP-C homodimers averaged over all homodimers belonging to the given dimer topology.
Contact probabilities equal to one correspond to the situation where given residues are in contact in all homodimers belonging to this cluster topology. Two residues were considered to be in contact, if any of their beads were closer than 6 Å. Only contact probabilities higher than 0.20 are shown for clarity.
Fig 8.
Contact probabilities of SP-C residues for all dimer topologies identified in this study.
The purple dashed line depicts the position of the putative AxxxG motif as reported by Kairys et al. [23].