All-atom molecular dynamics simulations of lung surfactant protein B: Structural features of SP-B promote lipid reorganization.
Lung surfactant protein B (SP-B), a 79 residue, hydrophobic protein from the saposin superfamily, plays an essential role in breathing. Because of the extreme hydrophobicity of SP-B, the experimental structure of this protein has not yet been determined. Here, we run all-atom molecular dynamics simulations using the OPLS-AA force field in GROMACS to study SP-B's structure and mechanisms for promoting lipid reorganization. Firstly, we find that the final structures indicate the need for some fine-tuning of the homology-based secondary structure predictions. Secondly, we find energetically feasible structures 1) with SP-B's helices in the plane of the bilayer, 2) with SP-B's helices inclined with respect to the bilayer, and 3) with SP-B in a closed structure interacting peripherally with the bilayer. Interestingly, SP-B structures that were bent at the hinge region between the pairs of helices promoted and/or stabilized defects in the lipid bilayer. Finally, particular salt bridge patterns and structural plasticity in the central loop and adjacent region of SP-B appeared to be involved in SP-B's lipid reorganization abilities.
Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.
Mohammad Hassan
MH
Khatami
Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.
Ivan
I
Saika-Voivod
Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada; Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada. Electronic address: vbooth@mun.ca.
Valerie
V
Booth
D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*
D008051:Lipid Bilayers; D037701:Pulmonary Surfactant-Associated Protein B
Bilayer diffusion; GROMACS; Lung surfactant protein; Molecular dynamics; POPC; SP-B