Molecular Dynamics Simulation of Saposin C-Membrane Binding

ABSTRACT

To understand the mechanism of Saposin C-membrane binding at low pH, several molecular dynamics (MD) simulations of saposin C with 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS 18; 1) or modified DOPS were performed in the default charge states at neutral pH or, based on the pKa calculations, with some protonated acidic residues to approximate low pH conditions. It was found that the electrostatic attraction between the protein-COO- and lipid-NH3 + groups played an important role in the binding process in addition to the electrostatic attraction between the lipid-COO- and protein-NH3 + groups. The two pairs of attractive interactions acted basically on the opposite sites of saposin C. Neutralization of the amino groups of the lipids enabled saposin C-binding with the membrane at neutral pH. The simulation results provide insight into the nature and mechanism of the Saposin C-membrane binding process at low pH.

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